The Experts below are selected from a list of 3705 Experts worldwide ranked by ideXlab platform
John S. D. Chan - One of the best experts on this subject based on the ideXlab platform.
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tubular deficiency of Heterogeneous Nuclear Ribonucleoprotein f elevates systolic blood pressure and induces glycosuria in mice
Scientific Reports, 2019Co-Authors: Kana N Miyata, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, Shuiling Zhao, Anindya Ghosh, John S. D. ChanAbstract:We reported previously that overexpression of Heterogeneous Nuclear Ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.
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Heterogeneous Nuclear Ribonucleoprotein f stimulates sirtuin 1 gene expression and attenuates nephropathy progression in diabetic mice
Diabetes, 2017Co-Authors: Yixuan Shi, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Anindya Ghosh, Jeanfrancois Cailhier, Jean Ethier, Jeanbaptiste Lattouf, John S. D. ChanAbstract:We investigated the mechanism of Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress, and nephropathy at age 20 weeks compared with their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs. Sirtuin-1, Foxo3α, and catalase expression were significantly decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3α with downregulation of acetylated p53 expression and prevented downregulation of Sirtuin-1 and Foxo3α expression in IRPTCs by high glucose plus palmitate. Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of Foxo3α and downregulation of acetylated p53 expression. hnRNP F stimulated Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter. Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3α than nondiabetic kidneys. Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes.
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overexpression of Heterogeneous Nuclear Ribonucleoprotein f stimulates renal ace 2 gene expression and prevents tgf β1 induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
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Overexpression of Heterogeneous Nuclear Ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
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Heterogeneous Nuclear Ribonucleoprotein f suppresses angiotensinogen gene expression and attenuates hypertension and kidney injury in diabetic mice
Diabetes, 2012Co-Authors: Shiaoying Chang, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, John S. D. ChanAbstract:We investigated the impact of Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) overexpression on angiotensinogen (Agt) gene expression, hypertension, and renal proximal tubular cell (RPTC) injury in high-glucose milieu both in vivo and in vitro. Diabetic Akita transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs were created, and the effects on systemic hypertension, Agt gene expression, renal hypertrophy, and interstitial fibrosis were studied. We also examined immortalized rat RPTCs stably transfected with control plasmid or plasmid containing hnRNP F cDNA in vitro. The results showed that hnRNP F overexpression attenuated systemic hypertension, suppressed Agt and transforming growth factor-β1 (TGF-β1) gene expression, and reduced urinary Agt and angiotensin II levels, renal hypertrophy, and glomerulotubular fibrosis in Akita hnRNP F-Tg mice. In vitro, hnRNP F overexpression prevented the high-glucose stimulation of Agt and TGF-β1 mRNA expression and cellular hypertrophy in RPTCs. These data suggest that hnRNP F plays a modulatory role and can ameliorate hypertension, renal hypertrophy, and interstitial fibrosis in diabetes. The underlying mechanism is mediated, at least in part, via the suppression of intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the treatment of hypertension and kidney injury in diabetes.
Shao-ling Zhang - One of the best experts on this subject based on the ideXlab platform.
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tubular deficiency of Heterogeneous Nuclear Ribonucleoprotein f elevates systolic blood pressure and induces glycosuria in mice
Scientific Reports, 2019Co-Authors: Kana N Miyata, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, Shuiling Zhao, Anindya Ghosh, John S. D. ChanAbstract:We reported previously that overexpression of Heterogeneous Nuclear Ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.
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Heterogeneous Nuclear Ribonucleoprotein f mediates insulin inhibition of bcl2 modifying factor expression and tubulopathy in diabetic kidney
Scientific Reports, 2019Co-Authors: Anindya Ghosh, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Chaosheng Lo, Shuiling Zhao, Hasna Maachi, Muhammad Abdul Lateef, Shao-ling ZhangAbstract:We investigated the molecular mechanism(s) by which insulin prevents Bcl2-modifying factor (Bmf)-induced renal proximal tubular cell (RPTC) apoptosis and loss in diabetic mice. Transgenic mice (Tg) mice specifically overexpressing human BMF in RPTCs and non-Tg littermates were studied at 10 to 20 weeks of age. Non-diabetic littermates, diabetic Akita mice +/− insulin implant, Akita Tg mice specifically overexpressing Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) in their RPTCs and immortalized rat renal proximal tubular cells (IRPTCs) were also studied. BMF-Tg mice exhibited higher systolic blood pressure, urinary albumin/creatinine ratio, RPTC apoptosis and urinary RPTCs than non-Tg mice. Insulin treatment in Akita mice and Akita mice overexpressing hnRNP F suppressed Bmf expression and RPTC apoptosis. In hyperinsulinemic-euglycemic wild type mice, renal Bmf expression was down-regulated with up-regulation of hnRNP F. In vitro, insulin inhibited high glucose-stimulation of Bmf expression, predominantly via p44/42 mitogen-activated protein kinase (MAPK) signaling. Transfection of p44/42 MAPK or hnRNP F small interfering RNA (siRNA) prevented insulin inhibition of Bmf expression. HnRNP F inhibited Bmf transcription via hnRNP F-responsive element in the Bmf promoter. Our results demonstrate that hnRNP F suppression of Bmf transcription is an important mechanism by which insulin protects RPTCs from apoptosis in diabetes.
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Heterogeneous Nuclear Ribonucleoprotein f stimulates sirtuin 1 gene expression and attenuates nephropathy progression in diabetic mice
Diabetes, 2017Co-Authors: Yixuan Shi, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Anindya Ghosh, Jeanfrancois Cailhier, Jean Ethier, Jeanbaptiste Lattouf, John S. D. ChanAbstract:We investigated the mechanism of Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress, and nephropathy at age 20 weeks compared with their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs. Sirtuin-1, Foxo3α, and catalase expression were significantly decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3α with downregulation of acetylated p53 expression and prevented downregulation of Sirtuin-1 and Foxo3α expression in IRPTCs by high glucose plus palmitate. Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of Foxo3α and downregulation of acetylated p53 expression. hnRNP F stimulated Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter. Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3α than nondiabetic kidneys. Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes.
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overexpression of Heterogeneous Nuclear Ribonucleoprotein f stimulates renal ace 2 gene expression and prevents tgf β1 induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
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Overexpression of Heterogeneous Nuclear Ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
Julie R. Ingelfinger - One of the best experts on this subject based on the ideXlab platform.
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tubular deficiency of Heterogeneous Nuclear Ribonucleoprotein f elevates systolic blood pressure and induces glycosuria in mice
Scientific Reports, 2019Co-Authors: Kana N Miyata, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, Shuiling Zhao, Anindya Ghosh, John S. D. ChanAbstract:We reported previously that overexpression of Heterogeneous Nuclear Ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.
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Heterogeneous Nuclear Ribonucleoprotein f mediates insulin inhibition of bcl2 modifying factor expression and tubulopathy in diabetic kidney
Scientific Reports, 2019Co-Authors: Anindya Ghosh, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Chaosheng Lo, Shuiling Zhao, Hasna Maachi, Muhammad Abdul Lateef, Shao-ling ZhangAbstract:We investigated the molecular mechanism(s) by which insulin prevents Bcl2-modifying factor (Bmf)-induced renal proximal tubular cell (RPTC) apoptosis and loss in diabetic mice. Transgenic mice (Tg) mice specifically overexpressing human BMF in RPTCs and non-Tg littermates were studied at 10 to 20 weeks of age. Non-diabetic littermates, diabetic Akita mice +/− insulin implant, Akita Tg mice specifically overexpressing Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) in their RPTCs and immortalized rat renal proximal tubular cells (IRPTCs) were also studied. BMF-Tg mice exhibited higher systolic blood pressure, urinary albumin/creatinine ratio, RPTC apoptosis and urinary RPTCs than non-Tg mice. Insulin treatment in Akita mice and Akita mice overexpressing hnRNP F suppressed Bmf expression and RPTC apoptosis. In hyperinsulinemic-euglycemic wild type mice, renal Bmf expression was down-regulated with up-regulation of hnRNP F. In vitro, insulin inhibited high glucose-stimulation of Bmf expression, predominantly via p44/42 mitogen-activated protein kinase (MAPK) signaling. Transfection of p44/42 MAPK or hnRNP F small interfering RNA (siRNA) prevented insulin inhibition of Bmf expression. HnRNP F inhibited Bmf transcription via hnRNP F-responsive element in the Bmf promoter. Our results demonstrate that hnRNP F suppression of Bmf transcription is an important mechanism by which insulin protects RPTCs from apoptosis in diabetes.
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Heterogeneous Nuclear Ribonucleoprotein f stimulates sirtuin 1 gene expression and attenuates nephropathy progression in diabetic mice
Diabetes, 2017Co-Authors: Yixuan Shi, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Anindya Ghosh, Jeanfrancois Cailhier, Jean Ethier, Jeanbaptiste Lattouf, John S. D. ChanAbstract:We investigated the mechanism of Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress, and nephropathy at age 20 weeks compared with their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs. Sirtuin-1, Foxo3α, and catalase expression were significantly decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3α with downregulation of acetylated p53 expression and prevented downregulation of Sirtuin-1 and Foxo3α expression in IRPTCs by high glucose plus palmitate. Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of Foxo3α and downregulation of acetylated p53 expression. hnRNP F stimulated Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter. Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3α than nondiabetic kidneys. Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes.
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overexpression of Heterogeneous Nuclear Ribonucleoprotein f stimulates renal ace 2 gene expression and prevents tgf β1 induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
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Overexpression of Heterogeneous Nuclear Ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
János G. Filep - One of the best experts on this subject based on the ideXlab platform.
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tubular deficiency of Heterogeneous Nuclear Ribonucleoprotein f elevates systolic blood pressure and induces glycosuria in mice
Scientific Reports, 2019Co-Authors: Kana N Miyata, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, Shuiling Zhao, Anindya Ghosh, John S. D. ChanAbstract:We reported previously that overexpression of Heterogeneous Nuclear Ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.
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Heterogeneous Nuclear Ribonucleoprotein f mediates insulin inhibition of bcl2 modifying factor expression and tubulopathy in diabetic kidney
Scientific Reports, 2019Co-Authors: Anindya Ghosh, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Chaosheng Lo, Shuiling Zhao, Hasna Maachi, Muhammad Abdul Lateef, Shao-ling ZhangAbstract:We investigated the molecular mechanism(s) by which insulin prevents Bcl2-modifying factor (Bmf)-induced renal proximal tubular cell (RPTC) apoptosis and loss in diabetic mice. Transgenic mice (Tg) mice specifically overexpressing human BMF in RPTCs and non-Tg littermates were studied at 10 to 20 weeks of age. Non-diabetic littermates, diabetic Akita mice +/− insulin implant, Akita Tg mice specifically overexpressing Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) in their RPTCs and immortalized rat renal proximal tubular cells (IRPTCs) were also studied. BMF-Tg mice exhibited higher systolic blood pressure, urinary albumin/creatinine ratio, RPTC apoptosis and urinary RPTCs than non-Tg mice. Insulin treatment in Akita mice and Akita mice overexpressing hnRNP F suppressed Bmf expression and RPTC apoptosis. In hyperinsulinemic-euglycemic wild type mice, renal Bmf expression was down-regulated with up-regulation of hnRNP F. In vitro, insulin inhibited high glucose-stimulation of Bmf expression, predominantly via p44/42 mitogen-activated protein kinase (MAPK) signaling. Transfection of p44/42 MAPK or hnRNP F small interfering RNA (siRNA) prevented insulin inhibition of Bmf expression. HnRNP F inhibited Bmf transcription via hnRNP F-responsive element in the Bmf promoter. Our results demonstrate that hnRNP F suppression of Bmf transcription is an important mechanism by which insulin protects RPTCs from apoptosis in diabetes.
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Heterogeneous Nuclear Ribonucleoprotein f stimulates sirtuin 1 gene expression and attenuates nephropathy progression in diabetic mice
Diabetes, 2017Co-Authors: Yixuan Shi, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Anindya Ghosh, Jeanfrancois Cailhier, Jean Ethier, Jeanbaptiste Lattouf, John S. D. ChanAbstract:We investigated the mechanism of Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress, and nephropathy at age 20 weeks compared with their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs. Sirtuin-1, Foxo3α, and catalase expression were significantly decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3α with downregulation of acetylated p53 expression and prevented downregulation of Sirtuin-1 and Foxo3α expression in IRPTCs by high glucose plus palmitate. Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of Foxo3α and downregulation of acetylated p53 expression. hnRNP F stimulated Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter. Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3α than nondiabetic kidneys. Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes.
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overexpression of Heterogeneous Nuclear Ribonucleoprotein f stimulates renal ace 2 gene expression and prevents tgf β1 induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
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Overexpression of Heterogeneous Nuclear Ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
Isabelle Chenier - One of the best experts on this subject based on the ideXlab platform.
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tubular deficiency of Heterogeneous Nuclear Ribonucleoprotein f elevates systolic blood pressure and induces glycosuria in mice
Scientific Reports, 2019Co-Authors: Kana N Miyata, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, Shuiling Zhao, Anindya Ghosh, John S. D. ChanAbstract:We reported previously that overexpression of Heterogeneous Nuclear Ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.
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Heterogeneous Nuclear Ribonucleoprotein f mediates insulin inhibition of bcl2 modifying factor expression and tubulopathy in diabetic kidney
Scientific Reports, 2019Co-Authors: Anindya Ghosh, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Chaosheng Lo, Shuiling Zhao, Hasna Maachi, Muhammad Abdul Lateef, Shao-ling ZhangAbstract:We investigated the molecular mechanism(s) by which insulin prevents Bcl2-modifying factor (Bmf)-induced renal proximal tubular cell (RPTC) apoptosis and loss in diabetic mice. Transgenic mice (Tg) mice specifically overexpressing human BMF in RPTCs and non-Tg littermates were studied at 10 to 20 weeks of age. Non-diabetic littermates, diabetic Akita mice +/− insulin implant, Akita Tg mice specifically overexpressing Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) in their RPTCs and immortalized rat renal proximal tubular cells (IRPTCs) were also studied. BMF-Tg mice exhibited higher systolic blood pressure, urinary albumin/creatinine ratio, RPTC apoptosis and urinary RPTCs than non-Tg mice. Insulin treatment in Akita mice and Akita mice overexpressing hnRNP F suppressed Bmf expression and RPTC apoptosis. In hyperinsulinemic-euglycemic wild type mice, renal Bmf expression was down-regulated with up-regulation of hnRNP F. In vitro, insulin inhibited high glucose-stimulation of Bmf expression, predominantly via p44/42 mitogen-activated protein kinase (MAPK) signaling. Transfection of p44/42 MAPK or hnRNP F small interfering RNA (siRNA) prevented insulin inhibition of Bmf expression. HnRNP F inhibited Bmf transcription via hnRNP F-responsive element in the Bmf promoter. Our results demonstrate that hnRNP F suppression of Bmf transcription is an important mechanism by which insulin protects RPTCs from apoptosis in diabetes.
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Heterogeneous Nuclear Ribonucleoprotein f stimulates sirtuin 1 gene expression and attenuates nephropathy progression in diabetic mice
Diabetes, 2017Co-Authors: Yixuan Shi, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Anindya Ghosh, Jeanfrancois Cailhier, Jean Ethier, Jeanbaptiste Lattouf, John S. D. ChanAbstract:We investigated the mechanism of Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db). Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans with T2D were also studied. The db/db mice developed hyperglycemia, oxidative stress, and nephropathy at age 20 weeks compared with their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs. Sirtuin-1, Foxo3α, and catalase expression were significantly decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3α with downregulation of acetylated p53 expression and prevented downregulation of Sirtuin-1 and Foxo3α expression in IRPTCs by high glucose plus palmitate. Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of Foxo3α and downregulation of acetylated p53 expression. hnRNP F stimulated Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter. Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F, SIRTUIN-1, and FOXO3α than nondiabetic kidneys. Our results demonstrate that hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation of Sirtuin-1 expression and signaling in diabetes.
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overexpression of Heterogeneous Nuclear Ribonucleoprotein f stimulates renal ace 2 gene expression and prevents tgf β1 induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.
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Overexpression of Heterogeneous Nuclear Ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes
Diabetologia, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Shiaoying Chang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether Heterogeneous Nuclear Ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes.