The Experts below are selected from a list of 1098 Experts worldwide ranked by ideXlab platform
John S. D. Chan - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
angiotensin 1 7 prevents systemic hypertension attenuates oxidative stress and tubulointerstitial fibrosis and normalizes renal angiotensin converting enzyme 2 and mas receptor expression in diabetic mice
Clinical Science, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice.
Clinical Science, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.
Diabetologia, 2013Co-Authors: Shaaban Abdo, Isabelle Chenier, A. Shamsuyarova, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita Mouse model of type 1 diabetes.
Akio Koizumi - One of the best experts on this subject based on the ideXlab platform.
-
Spontaneous development of ER stress that can lead to diabetes mellitus is associated with higher calcium-independent phospholipase A2 (iPLA2beta) expression: A role for regulation by SREBP-1
Journal of Biological Chemistry, 2009Co-Authors: Xiaoyong Lei, Akio Koizumi, Sheng Zhang, Suzanne E. Barbour, Alan Bohrer, Eric L. Ford, Feroz R. Papa, Sasanka RamanadhamAbstract:Abstract Our recent studies indicate that ER stress causes INS-1 cell apoptosis by a Ca2+-independent phospholipase A2 (iPLA2β)-mediated mechanism that promotes ceramide generation via sphingomyelin hydrolysis and subsequent activation of the intrinsic pathway. To elucidate the association between iPLA2β and ER stress, we compared β-cell lines generated from wild type (WT) and Akita mice. The Akita Mouse is a spontaneous model of ER stress that develops hyperglycemia/diabetes due to ER stress-induced β-cell apoptosis. Consistent with a pre-disposition to developing ER stress, basal pPERK and activated caspase-3 are higher in the Akita cells than WT cells. Interestingly, basal iPLA2β, mature SREBP-1 (mSREBP-1), phosphorylated Akt, and NSMase are higher, relative abundances of sphingomyelins lower, and mitochondrial membrane potential (∆Ψ) compromised in Akita cells, in comparison with WT cells. Exposure to thapsigargin accelerates ∆Ψ loss and apoptosis of Akita cells and is associated with increases in iPLA2β, mSREBP-1, and NSMase in both WT and Akita cells. Transfection of Akita cells with iPLA2β siRNA, however, suppresses NSMase message, ∆Ψ loss, and apoptosis. The iPLA2β gene contains a sterol regulatory element (SRE) and transfection with a dominant negative SREBP-1 reduces basal mSREBP-1 and iPLA2β in the Akita cells and suppresses increases in mSREBP-1 and iPLA2β due to thapsigargin. These findings suggest that ER stress leads to generation of mSREBP-1, which can bind to the SRE in the iPLA2β gene to promote its transcription. Consistent with this, SREBP-1, iPLA2β, and NSMase messages in Akita Mouse islets are higher than in WT islets.
-
Spontaneous Development of Endoplasmic Reticulum Stress That Can Lead to Diabetes Mellitus Is Associated with Higher Calcium-independent Phospholipase A2 Expression: A ROLE FOR REGULATION BY SREBP-1*
The Journal of biological chemistry, 2009Co-Authors: Xiaoyong Lei, Akio Koizumi, Sheng Zhang, Suzanne E. Barbour, Alan Bohrer, Eric L. Ford, Feroz R. Papa, Sasanka RamanadhamAbstract:Our recent studies indicate that endoplasmic reticulum (ER) stress causes INS-1 cell apoptosis by a Ca2+-independent phospholipase A2 (iPLA2β)-mediated mechanism that promotes ceramide generation via sphingomyelin hydrolysis and subsequent activation of the intrinsic pathway. To elucidate the association between iPLA2β and ER stress, we compared β-cell lines generated from wild type (WT) and Akita mice. The Akita Mouse is a spontaneous model of ER stress that develops hyperglycemia/diabetes due to ER stress-induced β-cell apoptosis. Consistent with a predisposition to developing ER stress, basal phosphorylated PERK and activated caspase-3 are higher in the Akita cells than WT cells. Interestingly, basal iPLA2β, mature SREBP-1 (mSREBP-1), phosphorylated Akt, and neutral sphingomyelinase (NSMase) are higher, relative abundances of sphingomyelins are lower, and mitochondrial membrane potential (ΔΨ) is compromised in Akita cells, in comparison with WT cells. Exposure to thapsigargin accelerates ΔΨ loss and apoptosis of Akita cells and is associated with increases in iPLA2β, mSREBP-1, and NSMase in both WT and Akita cells. Transfection of Akita cells with iPLA2β small interfering RNA, however, suppresses NSMase message, ΔΨ loss, and apoptosis. The iPLA2β gene contains a sterol-regulatory element, and transfection with a dominant negative SREBP-1 reduces basal mSREBP-1 and iPLA2β in the Akita cells and suppresses increases in mSREBP-1 and iPLA2β due to thapsigargin. These findings suggest that ER stress leads to generation of mSREBP-1, which can bind to the sterol-regulatory element in the iPLA2β gene to promote its transcription. Consistent with this, SREBP-1, iPLA2β, and NSMase messages in Akita Mouse islets are higher than in WT islets.
-
Proinsulin lacking the A7-B7 disulfide bond, Ins2Akita, tends to aggregate due to the exposed hydrophobic surface.
Biological Chemistry, 2005Co-Authors: Takeo Yoshinaga, Keisuke Nakatome, Jun-ichi Nozaki, Motoko Naitoh, Jun Hoseki, Hiroshi Kubota, Kazuhiro Nagata, Akio KoizumiAbstract:A single mutation (C96Y) in the Ins2 gene, which disrupts the A7-B7 disulfide bond, causes the diabetic phenotype in Akita mice. We biochemically analyzed the conformation of wild-type and Akita mutant recombinant proinsulins. Gel filtration chromatography and dynamic light scattering revealed that the apparent size of the mutant proinsulin molecules was significantly larger than that of wild-type proinsulin, even in the absence of intermolecular disulfide bonds. Titration with a hydrophobic probe, 1 -anilinonaphthalene-8-sulfonate, demonstrated that the mutant proinsulin was more hydrophobic than the wild type. In addition, circular dichroism studies revealed that the conformation of the mutant proinsulin was less stable than the wild type, which is consistent with the observation that hydrophobic residues are exposed on the surface of the proinsulin molecules. Studies with antiserum against the C-peptide of proinsulin indicated that the mutant proinsulin had an immunoreactivity that was at least one-tenth weaker than wild-type proinsulin, suggesting that the C-peptide of mutant proinsulin is buried inside the aggregate of the proinsulin molecule. These findings indicate that increased hydrophobicity of mutant proinsulin facilitates aggregate formation, providing a clue to the dominant negative effect in the Akita Mouse.
-
Endoplasmic reticulum stress induces Wfs1 gene expression in pancreatic β-cells via transcriptional activation
European Journal of Endocrinology, 2005Co-Authors: Kohei Ueda, Akio Koizumi, Takeo Yoshinaga, Jun-ichi Nozaki, June Kawano, Komei Takeda, Toshiaki Yujiri, Katsuya Tanabe, Takatoshi Anno, Masaru AkiyamaAbstract:Objective: The WFS1 gene encodes an endoplasmic reticulum (ER) membrane-embedded protein. Homozygous WFS1 gene mutations cause Wolfram syndrome, characterized by insulin-deficient diabetes mellitus and optic atropy. Pancreatic b-cells are selectively lost from the patient’s islets. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium homeostasis. Disturbances or overloading of these functions induces ER stress responses, including apoptosis. We speculated that WFS1 protein might be involved in these ER stress responses. Design and methods: Islet expression of the Wfs1 protein was analyzed immunohistochemically. Induction of Wfs1 upon ER stress was examined by Northern and Western blot analyses using three different models: human skin fibroblasts, Mouse pancreatic b-cell-derived MIN6 cells, and Akita Mouse-derived Ins2 96Y/Y insulinoma cells. The human WFS1 gene promoter-luciferase reporter analysis was also conducted. Result: Islet b-cells were the major site of Wfs1 expression. This expression was also found in d-cells, but not in a-cells. WFS1 expression was transcriptionally up-regulated by ER stress-inducing chemical insults. Treatment of fibroblasts and MIN6 cells with thapsigargin or tunicamycin increased WFS1 mRNA. WFS1 protein also increased in response to thapsigargin treatment in these cells. WFS1 gene expression was also increased in Ins2 96Y/Y insulinoma cells. In these cells, ER stress was intrinsically induced by mutant insulin expression. The WFS1 gene promoter-luciferase reporter system revealed that the human WFS1 promoter was activated by chemically induced ER stress in MIN6 cells, and that the promoter was more active in Ins2 96Y/Y cells than Ins2 wild/wild cells. Conclusion: Wfs1 expression, which is localized to b- and d-cells in pancreatic islets, increases in response to ER stress, suggesting a functional link between Wfs1 and ER stress.
-
targeted disruption of the chop gene delays endoplasmic reticulum stress mediated diabetes
Journal of Clinical Investigation, 2002Co-Authors: Seiichi Oyadomari, Akio Koizumi, Kiyoshi Takeda, Tomomi Gotoh, Shizuo Akira, Eiichi Araki, Masataka MoriAbstract:Overload of pancreatic β cells in conditions such as hyperglycemia, obesity, and long-term treatment with sulfonylureas leads to β cell exhaustion and type 2 diabetes. Because β cell mass declines under these conditions, apparently as a result of apoptosis, we speculated that overload kills β cells as a result of endoplasmic reticulum (ER) stress. The Akita Mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced β cell mass. In the development of diabetes in Akita mice, mRNAs for the ER chaperone Bip and the ER stress–associated apoptosis factor Chop were induced in the pancreas. Overexpression of the mutant insulin in Mouse MIN6 β cells induced Chop expression and led to apoptosis. Targeted disruption of the Chop gene delayed the onset of diabetes in heterozygous Akita mice by 8–10 weeks. We conclude that ER overload in β cells causes ER stress and leads to apoptosis via Chop induction. Our findings suggest a new therapeutic approach for preventing the onset of diabetes by inhibiting Chop induction or by increasing chaperone capacity in the ER.
Shaaban Abdo - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
angiotensin 1 7 prevents systemic hypertension attenuates oxidative stress and tubulointerstitial fibrosis and normalizes renal angiotensin converting enzyme 2 and mas receptor expression in diabetic mice
Clinical Science, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice.
Clinical Science, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.
Diabetologia, 2013Co-Authors: Shaaban Abdo, Isabelle Chenier, A. Shamsuyarova, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita Mouse model of type 1 diabetes.
Isabelle Chenier - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
angiotensin 1 7 prevents systemic hypertension attenuates oxidative stress and tubulointerstitial fibrosis and normalizes renal angiotensin converting enzyme 2 and mas receptor expression in diabetic mice
Clinical Science, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice.
Clinical Science, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.
Diabetologia, 2013Co-Authors: Shaaban Abdo, Isabelle Chenier, A. Shamsuyarova, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita Mouse model of type 1 diabetes.
Shao-ling Zhang - One of the best experts on this subject based on the ideXlab platform.
-
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.
-
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.
-
angiotensin 1 7 prevents systemic hypertension attenuates oxidative stress and tubulointerstitial fibrosis and normalizes renal angiotensin converting enzyme 2 and mas receptor expression in diabetic mice
Clinical Science, 2015Co-Authors: Chaosheng Lo, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Angiotensin-(1-7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice.
Clinical Science, 2015Co-Authors: Yixuan Shi, Shaaban Abdo, Isabelle Chenier, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, Ranjit Singh Padda, John S. D. ChanAbstract:We investigated the relationship between Ang-(1–7) [angiotensin-(1–7)] action, sHTN (systolic hypertension), oxidative stress, kidney injury, ACE2 (angiotensin-converting enzyme-2) and MasR [Ang-(1–7) receptor] expression in Type 1 diabetic Akita mice. Ang-(1–7) was administered daily [500 μg/kg of BW (body weight) per day, subcutaneously] to male Akita mice from 14 weeks of age with or without co-administration of an antagonist of the MasR, A779 (10 mg/kg of BW per day). The animals were killed at 20 weeks of age. Age-matched WT (wild-type) mice served as controls. Ang-(1–7) administration prevented sHTN and attenuated kidney injury (reduced urinary albumin/creatinine ratio, glomerular hyperfiltration, renal hypertrophy and fibrosis, and tubular apoptosis) without affecting blood glucose levels in Akita mice. Ang-(1–7) also attenuated renal oxidative stress and the expression of oxidative stress-inducible proteins (NADPH oxidase 4, nuclear factor erythroid 2-related factor 2, haem oxygenase 1), pro-hypertensive proteins (angiotensinogen, angiotensin-converting enzyme, sodium/hydrogen exchanger 3) and profibrotic proteins (transforming growth factor-β1 and collagen IV), and increased the expression of anti-hypertensive proteins (ACE2 and MasR) in Akita Mouse kidneys. These effects were reversed by A779. Our data suggest that Ang-(1–7) plays a protective role in sHTN and RPTC (renal proximal tubular cell) injury in diabetes, at least in part, through decreasing renal oxidative stress-mediated signalling and normalizing ACE2 and MasR expression.
-
Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice.
Diabetologia, 2013Co-Authors: Shaaban Abdo, Isabelle Chenier, A. Shamsuyarova, János G. Filep, Julie R. Ingelfinger, Shao-ling Zhang, John S. D. ChanAbstract:Aims/hypothesis We investigated whether heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K) mediate insulin inhibition of renal Agt expression and prevention of hypertension and kidney injury in an Akita Mouse model of type 1 diabetes.
