Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy

Abstract Autophagy plays a key role in the pathogenesis of kidney diseases, however its role in diabetic nephropathy (DN), and particularly in kidney glomerular mesangial cells (MCs) is not very clear. Transforming Growth Factor- β1 (TGF-β), a key player in the pathogenesis of DN, regulates expressi...

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Autores principales:	Supriya Deshpande, Maryam Abdollahi, Mei Wang, Linda Lanting, Mitsuo Kato, Rama Natarajan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5255ac3e313a425f815d571d439fd77b
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spelling	oai:doaj.org-article:5255ac3e313a425f815d571d439fd77b2021-12-02T15:08:28ZReduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy10.1038/s41598-018-25295-x2045-2322https://doaj.org/article/5255ac3e313a425f815d571d439fd77b2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25295-xhttps://doaj.org/toc/2045-2322Abstract Autophagy plays a key role in the pathogenesis of kidney diseases, however its role in diabetic nephropathy (DN), and particularly in kidney glomerular mesangial cells (MCs) is not very clear. Transforming Growth Factor- β1 (TGF-β), a key player in the pathogenesis of DN, regulates expression of various microRNAs (miRNAs), some of which are known to regulate the expression of autophagy genes. Here we demonstrate that miR-192, induced by TGF-β signaling, plays an important role in regulating autophagy in DN. The expression of key autophagy genes was decreased in kidneys of streptozotocin-injected type-1 and type-2 (db/db) diabetic mice and this was reversed by treatment with Locked Nucleic Acid (LNA) modified miR-192 inhibitors. Changes in autophagy gene expression were also attenuated in kidneys of diabetic miR-192-KO mice. In vitro studies using mouse glomerular mesangial cells (MMCs) also showed a decrease in autophagy gene expression with TGF-β treatment. miR-192 mimic oligonucleotides also decreased the expression of certain autophagy genes. These results demonstrate that TGF-β and miR-192 decrease autophagy in MMCs under diabetic conditions and this can be reversed by inhibition or deletion of miR-192, further supporting miR-192 as a useful therapeutic target for DN.Supriya DeshpandeMaryam AbdollahiMei WangLinda LantingMitsuo KatoRama NatarajanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Supriya Deshpande Maryam Abdollahi Mei Wang Linda Lanting Mitsuo Kato Rama Natarajan Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy
description	Abstract Autophagy plays a key role in the pathogenesis of kidney diseases, however its role in diabetic nephropathy (DN), and particularly in kidney glomerular mesangial cells (MCs) is not very clear. Transforming Growth Factor- β1 (TGF-β), a key player in the pathogenesis of DN, regulates expression of various microRNAs (miRNAs), some of which are known to regulate the expression of autophagy genes. Here we demonstrate that miR-192, induced by TGF-β signaling, plays an important role in regulating autophagy in DN. The expression of key autophagy genes was decreased in kidneys of streptozotocin-injected type-1 and type-2 (db/db) diabetic mice and this was reversed by treatment with Locked Nucleic Acid (LNA) modified miR-192 inhibitors. Changes in autophagy gene expression were also attenuated in kidneys of diabetic miR-192-KO mice. In vitro studies using mouse glomerular mesangial cells (MMCs) also showed a decrease in autophagy gene expression with TGF-β treatment. miR-192 mimic oligonucleotides also decreased the expression of certain autophagy genes. These results demonstrate that TGF-β and miR-192 decrease autophagy in MMCs under diabetic conditions and this can be reversed by inhibition or deletion of miR-192, further supporting miR-192 as a useful therapeutic target for DN.
format	article
author	Supriya Deshpande Maryam Abdollahi Mei Wang Linda Lanting Mitsuo Kato Rama Natarajan
author_facet	Supriya Deshpande Maryam Abdollahi Mei Wang Linda Lanting Mitsuo Kato Rama Natarajan
author_sort	Supriya Deshpande
title	Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy
title_short	Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy
title_full	Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy
title_fullStr	Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy
title_full_unstemmed	Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy
title_sort	reduced autophagy by a microrna-mediated signaling cascade in diabetes-induced renal glomerular hypertrophy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5255ac3e313a425f815d571d439fd77b
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Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy

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