The renoprotective role of autophagy activation in proximal tubular epithelial cells in diabetic nephropathy

Journal of Diabetes and Its Complications
Ying XuQiang Wan

Abstract

With intensive investigations recently, autophagy is hoped to be a potential therapeutic target to prevent or alleviate diabetic nephropathy (DN). Our previous study revealed that lipotoxicity participated in epithelial-to-mesenchymal transition (EMT) of proximal tubular epithelial cells (PTECs) under diabetic conditions. Based on evidences that autophagy and lipid metabolism are closely related, we investigated autophagy under diabetic conditions and how it contributed in the lipotoxicity and EMT. In high-glucose-cultured PTECs, we found that Beclin1 and LC3-II were elevated, while p62 was decreased. These results indicate that autophagy activity was elevated under diabetic conditions. Autophagy deficiency induced by autophagy inhibitors, chloroquine diphosphate (CQ) and 3-Methyladenine (3-MA), and by Atg5 siRNA transfection exacerbated lipid accumulation and EMT. This supports that the elevated autophagy activity acts as a renoprotective response under diabetic conditions. Treatment of rapamycin, which is a mammalian target of rapamycin (mTOR) receptor-specific inhibitor and a known autophagy activator, attenuated high-glucose-induced lipid accumulation and EMT. The Atg5 silence counteracted the protective effect of rapamycin...Continue Reading

References

Jan 1, 1997·Kidney International·G RemuzziA Benigni
Mar 28, 1998·The Journal of Biological Chemistry·Takeshi Noda, Y Ohsumi
Sep 12, 1998·Kidney International·K A Nath
Dec 21, 2005·Biochemical and Biophysical Research Communications·Masayoshi SakaguchiAtsunori Kashiwagi
Nov 10, 2007·The American Journal of Pathology·Kavithalakshmi SataranatarajanBalakuntalam S Kasinath
May 30, 2008·Kidney International·Sudharsan Periyasamy-ThandavanZheng Dong
Mar 17, 2009·Biochemical and Biophysical Research Communications·Masahiro ShibataYasuo Uchiyama
Feb 6, 2010·Biochemical and Biophysical Research Communications·Masahiro ShibataYasuo Uchiyama
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine
Nov 19, 2010·Kidney International·Tobias B HuberE Wolfgang Kuehn
Jun 21, 2011·Small GTPases·Johanna Ivaska
Nov 17, 2011·Nephrology·Wan-Young KimYong Kyun Kim
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun
Jan 17, 2013·Autophagy·Louis R LapierreAlicia Meléndez
Oct 5, 2013·Journal of the American Society of Nephrology : JASN·Kosuke YamaharaTakashi Uzu
Feb 4, 2014·Seminars in Nephrology·Shinji KumeDaisuke Koya
Feb 4, 2014·Seminars in Nephrology·Yan Ding, Mary E Choi
Mar 19, 2014·Acta Pharmacologica Sinica·Nan MaoJun-ming Fan
Mar 26, 2014·Nature Reviews. Endocrinology·Kook Hwan Kim, Myung-Shik Lee
Jun 10, 2014·Lancet·Yuankai Shi, Frank B Hu

Citations

Aug 11, 2016·Metabolism: Clinical and Experimental·Wei XinQiang Wan
Jun 26, 2020·Journal of Cellular and Molecular Medicine·Hui Juan ZhengWei Jing Liu
Dec 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Yu-Lin ManHong Cheng
May 29, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Paola PontrelliLoreto Gesualdo
Aug 18, 2020·The Journal of Clinical Investigation·Zhengwei MaZheng Dong
Jul 15, 2020·International Urology and Nephrology·Elias A T KochNakhoul Nakhoul

Related Concepts

Chloroquine diphosphate, (-)-isomer
3-methyladenine
P62 protein, human
MAP1LC3A protein, human
BECN1 protein, human
ATG5 protein, human
FRAP1 protein, human
Adenine
Programmed Cell Death, Type II
Nivaquine

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