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Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro

It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN). Here we used shRNA transfection to knockdown the insulin receptor (IR) gene in cultured human immortalized podocytes as an in vitro in...

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Autores principales: Xu, Ying, Zhou, Qi, Xin, Wei, Li, Zhaoping, Chen, Liyong, Wan, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830256/
https://www.ncbi.nlm.nih.gov/pubmed/27077005
http://dx.doi.org/10.7717/peerj.1888
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author Xu, Ying
Zhou, Qi
Xin, Wei
Li, Zhaoping
Chen, Liyong
Wan, Qiang
author_facet Xu, Ying
Zhou, Qi
Xin, Wei
Li, Zhaoping
Chen, Liyong
Wan, Qiang
author_sort Xu, Ying
collection PubMed
description It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN). Here we used shRNA transfection to knockdown the insulin receptor (IR) gene in cultured human immortalized podocytes as an in vitro insulin resistant model. Autophagy related proteins LC3, Beclin, and p62 as well as nephrin, a podocyte injury marker, were assessed using western blot and immunofluorescence staining. Our results show that autophagy is suppressed when podocytes lose insulin sensitivity and that treatment of rapamycin, an mTOR specific inhibitor, could attenuate insulin resistance induced podocytes injury via autophagy activation. The present study deepens our understanding of the role of autophagy in the pathogenesis of DN.
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spelling pubmed-48302562016-04-13 Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro Xu, Ying Zhou, Qi Xin, Wei Li, Zhaoping Chen, Liyong Wan, Qiang PeerJ Cell Biology It is unknown whether autophagy activity is altered in insulin resistant podocytes and whether autophagy could be a therapeutic target for diabetic nephropathy (DN). Here we used shRNA transfection to knockdown the insulin receptor (IR) gene in cultured human immortalized podocytes as an in vitro insulin resistant model. Autophagy related proteins LC3, Beclin, and p62 as well as nephrin, a podocyte injury marker, were assessed using western blot and immunofluorescence staining. Our results show that autophagy is suppressed when podocytes lose insulin sensitivity and that treatment of rapamycin, an mTOR specific inhibitor, could attenuate insulin resistance induced podocytes injury via autophagy activation. The present study deepens our understanding of the role of autophagy in the pathogenesis of DN. PeerJ Inc. 2016-04-11 /pmc/articles/PMC4830256/ /pubmed/27077005 http://dx.doi.org/10.7717/peerj.1888 Text en ©2016 Xu et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Cell Biology
Xu, Ying
Zhou, Qi
Xin, Wei
Li, Zhaoping
Chen, Liyong
Wan, Qiang
Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
title Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
title_full Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
title_fullStr Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
title_full_unstemmed Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
title_short Autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
title_sort autophagy downregulation contributes to insulin resistance mediated injury in insulin receptor knockout podocytes in vitro
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830256/
https://www.ncbi.nlm.nih.gov/pubmed/27077005
http://dx.doi.org/10.7717/peerj.1888
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