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Helen K. W. Law - One of the best experts on this subject based on the ideXlab platform.
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trehalose an mtor independent autophagy inducer alleviates human Podocyte injury after puromycin aminonucleoside treatment
PLOS ONE, 2014Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, M Saleem, Helen K. W. LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophagy in human Podocytes and showed cytoprotective effects in PAN-treated Podocytes.
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The cytoprotective role of autophagy in puromycin aminonucleoside treated human Podocytes
Biochemical and biophysical research communications, 2013Co-Authors: Yu-lin Kang, Moin A. Saleem, Kwok Wah Chan, Benjamin Yat-ming Yung, Helen K. W. LawAbstract:Autophagy is a ubiquitous catabolic process involving degradation of damaged organelles and protein aggregates. It shows cytoprotective effects in many cell types and helps to maintain cell homeostasis. In many glomerular diseases, Podocyte damage leads to the disruption of the renal filtration barrier and subsequent proteinuria. Puromycin aminonucleoside (PAN) which induces Podocyte apoptosis in vitro and in vivo is widely used for studying the pathophysiology of glomerular diseases. It has been shown that PAN induces autophagy in Podocytes. However, the relationship between autophagy and apoptosis in PAN treated human Podocytes is not known and the role of PAN-induced autophagy in Podocyte survival remains unclear. Here we demonstrate that PAN induced autophagy in human Podocytes prior to apoptosis which was featured with the activation of mTOR complex 1 (mTORC1). When the PAN-induced autophagy was inhibited by 3-methyladenine (3-MA) or chloroquine (CQ), Podocyte apoptosis increased significantly along with the elevation of active caspase-3. Under such circumstance, the Podocyte cytoskeleton was also disrupted. Collectively, our results suggested that the induced autophagy may be an early adaptive cytoprotective mechanism for Podocyte survival after PAN treatment.
Yu-lin Kang - One of the best experts on this subject based on the ideXlab platform.
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Trehalose, an mtor independent autophagy inducer, alleviates human Podocyte injury after puromycin aminonucleoside treatment
2016Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, Moin Ahson Saleem, Helen Ka-wai LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophag
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trehalose an mtor independent autophagy inducer alleviates human Podocyte injury after puromycin aminonucleoside treatment
PLOS ONE, 2014Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, M Saleem, Helen K. W. LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophagy in human Podocytes and showed cytoprotective effects in PAN-treated Podocytes.
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The cytoprotective role of autophagy in puromycin aminonucleoside treated human Podocytes
Biochemical and biophysical research communications, 2013Co-Authors: Yu-lin Kang, Moin A. Saleem, Kwok Wah Chan, Benjamin Yat-ming Yung, Helen K. W. LawAbstract:Autophagy is a ubiquitous catabolic process involving degradation of damaged organelles and protein aggregates. It shows cytoprotective effects in many cell types and helps to maintain cell homeostasis. In many glomerular diseases, Podocyte damage leads to the disruption of the renal filtration barrier and subsequent proteinuria. Puromycin aminonucleoside (PAN) which induces Podocyte apoptosis in vitro and in vivo is widely used for studying the pathophysiology of glomerular diseases. It has been shown that PAN induces autophagy in Podocytes. However, the relationship between autophagy and apoptosis in PAN treated human Podocytes is not known and the role of PAN-induced autophagy in Podocyte survival remains unclear. Here we demonstrate that PAN induced autophagy in human Podocytes prior to apoptosis which was featured with the activation of mTOR complex 1 (mTORC1). When the PAN-induced autophagy was inhibited by 3-methyladenine (3-MA) or chloroquine (CQ), Podocyte apoptosis increased significantly along with the elevation of active caspase-3. Under such circumstance, the Podocyte cytoskeleton was also disrupted. Collectively, our results suggested that the induced autophagy may be an early adaptive cytoprotective mechanism for Podocyte survival after PAN treatment.
Stuart J. Shankland - One of the best experts on this subject based on the ideXlab platform.
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parietal epithelial cell differentiation to a Podocyte fate in the aged mouse kidney
Aging, 2020Co-Authors: Natalya V Kaverina, Jeffrey W Pippin, Diana G Eng, Jeffrey H Miner, Stuart J. ShanklandAbstract:Healthy aging is typified by a progressive and absolute loss of Podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a Podocyte fate with aging, dual reporter PEC-rtTA|LC1|tdTomato|Nphs1-FLPo|FRT-EGFP mice were generated. PECs were inducibly labeled with a tdTomato reporter, and Podocytes were constitutively labeled with an EGFP reporter. With advancing age (14 and 24 months) glomeruli in the juxta-medullary cortex (JMC) were more severely injured than those in the outer cortex (OC). In aged mice (24m), injured glomeruli with lower Podocyte number (41% decrease), showed more PEC migration and differentiation to a Podocyte fate than mildly injured or healthy glomeruli. PECs differentiated to a Podocyte fate had ultrastructural features of Podocytes and co-expressed the Podocyte markers podocin, nephrin, p57 and VEGF164, but not markers of mesangial (Perlecan) or endothelial (ERG) cells. PECs differentiated to a Podocyte fate did not express CD44, a marker of PEC activation. Taken together, we demonstrate that a subpopulation of PECs differentiate to a Podocyte fate predominantly in injured glomeruli in mice of advanced age.
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kruppel like factor 15 mediates glucocorticoid induced restoration of Podocyte differentiation markers
Journal of The American Society of Nephrology, 2017Co-Authors: Sandeep K Mallipattu, Stuart J. Shankland, Agnieszka B. Bialkowska, Yiqing Guo, Monica P Revelo, Lucia Roapena, Timothy Miller, Jason Ling, Chelsea Estrada, Mukesh K. JainAbstract:Podocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the Podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores Podocyte differentiation markers and normal ultrastructure and improves cell survival in murine Podocytes. We previously determined that Kruppel-like factor 15 (KLF15), a kidney-enriched zinc finger transcription factor, is required for restoring Podocyte differentiation markers in mice and human Podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine Podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15 In three independent proteinuric murine models, Podocyte-specific loss of Klf15 abrogated dexamethasone-induced Podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human Podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human Podocytes. Finally, the level of KLF15 expression in the Podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the Podocyte.
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the antiviral cytokines ifn α and ifn β modulate parietal epithelial cells and promote Podocyte loss implications for ifn toxicity viral glomerulonephritis and glomerular regeneration
American Journal of Pathology, 2013Co-Authors: Adriana Migliorini, Shrikant R Mulay, Maria Lucia Angelotti, Onkar O Kulkarni, Jana Demleitner, Alexander Dietrich, Costanza Sagrinati, Lara Ballerini, Anna Peired, Stuart J. ShanklandAbstract:Interferon (IFN)-α and IFN-β are the central regulators of antiviral immunity but little is known about their roles in viral glomerulonephritis (eg, HIV nephropathy). We hypothesized that IFN-α and IFN-β would trigger local inflammation and Podocyte loss. We found that both IFNs consistently activated human and mouse Podocytes and parietal epithelial cells to express numerous IFN-stimulated genes. However, only IFN-β significantly induced Podocyte death and increased the permeability of Podocyte monolayers. In contrast, only IFN-α caused cell-cycle arrest and inhibited the migration of parietal epithelial cells. Both IFNs suppressed renal progenitor differentiation into mature Podocytes. In Adriamycin nephropathy, injections with either IFN-α or IFN-β aggravated proteinuria, macrophage influx, and glomerulosclerosis. A detailed analysis showed that only IFN-β induced Podocyte mitosis. This did not, however, lead to proliferation, but was associated with Podocyte loss via Podocyte detachment and/or mitotic Podocyte death (mitotic catastrophe). We did not detect TUNEL-positive Podocytes. Thus, IFN-α and IFN-β have both common and differential effects on Podocytes and parietal epithelial cells, which together promote glomerulosclerosis by enhancing Podocyte loss while suppressing Podocyte regeneration from local progenitors.
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the Podocyte s response to injury role in proteinuria and glomerulosclerosis
Kidney International, 2006Co-Authors: Stuart J. ShanklandAbstract:The terminally differentiated Podocyte, also called glomerular visceral epithelial cell, are highly specialized cells. They function as a critical size and charge barrier to prevent proteinuria. Podocytes are injured in diabetic and non-diabetic renal diseases. The clinical signature of Podocyte injury is proteinuria, with or without loss of renal function owing to glomerulosclerosis. There is an exciting and expanding literature showing that hereditary, congenital, or acquired abnormalities in the molecular anatomy of Podocytes leads to proteinuria, and at times, glomerulosclerosis. The change in Podocyte shape, called effacement, is not simply a passive process following injury, but is owing to a complex interplay of proteins that comprise the molecular anatomy of the different protein domains of Podocytes. These will be discussed in this review. Recent studies have also highlighted that a reduction in Podocyte number directly causes proteinuria and glomerulosclerosis. This is owing to several factors, including the relative inability for these cells to proliferate, detachment, and apoptosis. The mechanisms of these events are being elucidated, and are discussed in this review. It is the hope that by delineating the events following injury to Podocytes, therapies might be developed to reduce the burden of proteinuric renal diseases.
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glial cell line derived neurotrophic factor and its receptor ret is a novel ligand receptor complex critical for survival response during Podocyte injury
Journal of The American Society of Nephrology, 2006Co-Authors: Cynthia C Tsui, Stuart J. Shankland, Brian A PierchalaAbstract:Glomerulosclerosis correlates with a reduction in Podocyte number that occurs through mechanisms that include apoptosis. Whether glial cell line-derived neurotrophic factor (GDNF), a growth factor that is critical for neural and renal development, is a survival factor for injured Podocytes was investigated. Ret, the GDNF receptor tyrosine kinase, was upregulated in Podocytes in the passive Heymann nephritis and puromycin aminonucleoside (PA) nephrosis rat models of Podocyte injury. In addition, Ret mRNA and protein were upregulated in mouse Podocytes in vitro after injury that was induced by sublytic C5b-9 and PA. GDNF, which also was induced during Podocyte injury, inhibited significantly the apoptosis of Podocytes that was induced by ultraviolet C irradiation. Knockdown of Ret expression by small interference RNA in Podocytes exacerbated apoptosis that was induced by both ultraviolet C and PA. Ret knockdown, upon injury, decreased AKT phosphorylation, suggesting that the phosphoinositol-3 kinase/AKT pathway mediated the survival effect of GDNF on Podocytes. Consistent with this hypothesis, the selective phosphoinositol-3 kinase inhibitor LY294002 blocked the survival-promoting effects of GDNF. In conclusion, GDNF is a novel Podocyte survival factor. Furthermore, Ret is highly upregulated during Podocyte injury in vitro and in vivo, suggesting that Ret activation is a critical adaptive response for Podocyte remodeling and repair.
Kwok Wah Chan - One of the best experts on this subject based on the ideXlab platform.
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Trehalose, an mtor independent autophagy inducer, alleviates human Podocyte injury after puromycin aminonucleoside treatment
2016Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, Moin Ahson Saleem, Helen Ka-wai LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophag
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trehalose an mtor independent autophagy inducer alleviates human Podocyte injury after puromycin aminonucleoside treatment
PLOS ONE, 2014Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, M Saleem, Helen K. W. LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophagy in human Podocytes and showed cytoprotective effects in PAN-treated Podocytes.
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The cytoprotective role of autophagy in puromycin aminonucleoside treated human Podocytes
Biochemical and biophysical research communications, 2013Co-Authors: Yu-lin Kang, Moin A. Saleem, Kwok Wah Chan, Benjamin Yat-ming Yung, Helen K. W. LawAbstract:Autophagy is a ubiquitous catabolic process involving degradation of damaged organelles and protein aggregates. It shows cytoprotective effects in many cell types and helps to maintain cell homeostasis. In many glomerular diseases, Podocyte damage leads to the disruption of the renal filtration barrier and subsequent proteinuria. Puromycin aminonucleoside (PAN) which induces Podocyte apoptosis in vitro and in vivo is widely used for studying the pathophysiology of glomerular diseases. It has been shown that PAN induces autophagy in Podocytes. However, the relationship between autophagy and apoptosis in PAN treated human Podocytes is not known and the role of PAN-induced autophagy in Podocyte survival remains unclear. Here we demonstrate that PAN induced autophagy in human Podocytes prior to apoptosis which was featured with the activation of mTOR complex 1 (mTORC1). When the PAN-induced autophagy was inhibited by 3-methyladenine (3-MA) or chloroquine (CQ), Podocyte apoptosis increased significantly along with the elevation of active caspase-3. Under such circumstance, the Podocyte cytoskeleton was also disrupted. Collectively, our results suggested that the induced autophagy may be an early adaptive cytoprotective mechanism for Podocyte survival after PAN treatment.
Benjamin Yat-ming Yung - One of the best experts on this subject based on the ideXlab platform.
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Trehalose, an mtor independent autophagy inducer, alleviates human Podocyte injury after puromycin aminonucleoside treatment
2016Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, Moin Ahson Saleem, Helen Ka-wai LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophag
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trehalose an mtor independent autophagy inducer alleviates human Podocyte injury after puromycin aminonucleoside treatment
PLOS ONE, 2014Co-Authors: Yu-lin Kang, Kwok Wah Chan, Benjamin Yat-ming Yung, M Saleem, Helen K. W. LawAbstract:Glomerular diseases are commonly characterized by Podocyte injury including apoptosis, actin cytoskeleton rearrangement and detachment. However, the strategies for preventing Podocyte damage remain insufficient. Recently autophagy has been regarded as a vital cytoprotective mechanism for keeping Podocyte homeostasis. Thus, it is reasonable to utilize this mechanism to attenuate Podocyte injury. Trehalose, a natural disaccharide, is an mTOR independent autophagy inducer. It is unclear whether trehalose alleviates Podocyte injury. Therefore, we investigated the efficacy of trehalose in puromycin aminonucleoside (PAN)-treated Podocytes which mimic cell damage in minimal change nephrotic syndrome in vitro. Human conditional immortalized Podocytes were treated with trehalose with or without PAN. Autophagy was investigated by immunofluorescence staining for LC3 puncta and Western blotting for LC3, Atg5, p-AMPK, p-mTOR and its substrates. Podocyte apoptosis and necrosis were evaluated by flow cytometry and by measuring lactate dehydrogenase activity respectively. We also performed migration assay to examine Podocyte recovery. It was shown that trehalose induced Podocyte autophagy in an mTOR independent manner and without reactive oxygen species involvement. Podocyte apoptosis significantly decreased after trehalose treatment, while the inhibition of trehalose-induced autophagy abolished its protective effect. Additionally, the disrupted actin cytoskeleton of Podocytes was partially reversed by trehalose, accompanying with less lamellipodias and diminished motility. These results suggested that trehalose induced autophagy in human Podocytes and showed cytoprotective effects in PAN-treated Podocytes.
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The cytoprotective role of autophagy in puromycin aminonucleoside treated human Podocytes
Biochemical and biophysical research communications, 2013Co-Authors: Yu-lin Kang, Moin A. Saleem, Kwok Wah Chan, Benjamin Yat-ming Yung, Helen K. W. LawAbstract:Autophagy is a ubiquitous catabolic process involving degradation of damaged organelles and protein aggregates. It shows cytoprotective effects in many cell types and helps to maintain cell homeostasis. In many glomerular diseases, Podocyte damage leads to the disruption of the renal filtration barrier and subsequent proteinuria. Puromycin aminonucleoside (PAN) which induces Podocyte apoptosis in vitro and in vivo is widely used for studying the pathophysiology of glomerular diseases. It has been shown that PAN induces autophagy in Podocytes. However, the relationship between autophagy and apoptosis in PAN treated human Podocytes is not known and the role of PAN-induced autophagy in Podocyte survival remains unclear. Here we demonstrate that PAN induced autophagy in human Podocytes prior to apoptosis which was featured with the activation of mTOR complex 1 (mTORC1). When the PAN-induced autophagy was inhibited by 3-methyladenine (3-MA) or chloroquine (CQ), Podocyte apoptosis increased significantly along with the elevation of active caspase-3. Under such circumstance, the Podocyte cytoskeleton was also disrupted. Collectively, our results suggested that the induced autophagy may be an early adaptive cytoprotective mechanism for Podocyte survival after PAN treatment.
