MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy

Renal tubulointerstitial fibrosis (TIF) is a major feature of diabetic nephropathy (DN). There is increasing evidence demonstrating that microRNAs act as key players in the regulation of autophagy and are involved in DN. However, the exact link among microRNAs, autophagy, and TIF in DN is largely un...

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Main Authors: Yingying Zhang, Siqi Zhao, Depei Wu, Xingmei Liu, Mingjun Shi, Yuanyuan Wang, Fan Zhang, Jing Ding, Ying Xiao, Bing Guo
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/4728645
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author Yingying Zhang
Siqi Zhao
Depei Wu
Xingmei Liu
Mingjun Shi
Yuanyuan Wang
Fan Zhang
Jing Ding
Ying Xiao
Bing Guo
author_facet Yingying Zhang
Siqi Zhao
Depei Wu
Xingmei Liu
Mingjun Shi
Yuanyuan Wang
Fan Zhang
Jing Ding
Ying Xiao
Bing Guo
author_sort Yingying Zhang
collection DOAJ
description Renal tubulointerstitial fibrosis (TIF) is a major feature of diabetic nephropathy (DN). There is increasing evidence demonstrating that microRNAs act as key players in the regulation of autophagy and are involved in DN. However, the exact link among microRNAs, autophagy, and TIF in DN is largely unknown. In this study, our results showed that TIF was observed in DN rats together with obvious autophagy suppression. Moreover, microRNA-22 (miR-22) was upregulated and associated with reduced expression of its target gene phosphatase and tensin homolog (PTEN) in both the kidneys of DN rats and high glucose-cultured NRK-52E cells. Intriguingly, induction of autophagy by rapamycin antagonized high glucose-induced collagen IV (Col IV) and α-SMA expression. In addition, ectopic expression of miR-22 suppressed autophagic flux and induced the expression of Col IV and α-SMA, whereas the inhibition of endogenous miR-22 effectively relieved high glucose-induced autophagy suppression and the expression of Col IV and α-SMA in NRK-52E cells. Overexpression of PTEN protectively antagonized high glucose- and miR-22-induced autophagy suppression and the expression of Col IV. Therefore, our findings indicated that miR-22 may promote TIF by suppressing autophagy partially via targeting PTEN and represents a novel and promising therapeutic target for DN.
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institution Kabale University
issn 2314-6745
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publisher Wiley
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series Journal of Diabetes Research
spelling doaj-art-6ecd1269a7e145b1914be62f07478f632025-02-03T06:01:35ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/47286454728645MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic NephropathyYingying Zhang0Siqi Zhao1Depei Wu2Xingmei Liu3Mingjun Shi4Yuanyuan Wang5Fan Zhang6Jing Ding7Ying Xiao8Bing Guo9Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaDepartment of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, ChinaRenal tubulointerstitial fibrosis (TIF) is a major feature of diabetic nephropathy (DN). There is increasing evidence demonstrating that microRNAs act as key players in the regulation of autophagy and are involved in DN. However, the exact link among microRNAs, autophagy, and TIF in DN is largely unknown. In this study, our results showed that TIF was observed in DN rats together with obvious autophagy suppression. Moreover, microRNA-22 (miR-22) was upregulated and associated with reduced expression of its target gene phosphatase and tensin homolog (PTEN) in both the kidneys of DN rats and high glucose-cultured NRK-52E cells. Intriguingly, induction of autophagy by rapamycin antagonized high glucose-induced collagen IV (Col IV) and α-SMA expression. In addition, ectopic expression of miR-22 suppressed autophagic flux and induced the expression of Col IV and α-SMA, whereas the inhibition of endogenous miR-22 effectively relieved high glucose-induced autophagy suppression and the expression of Col IV and α-SMA in NRK-52E cells. Overexpression of PTEN protectively antagonized high glucose- and miR-22-induced autophagy suppression and the expression of Col IV. Therefore, our findings indicated that miR-22 may promote TIF by suppressing autophagy partially via targeting PTEN and represents a novel and promising therapeutic target for DN.http://dx.doi.org/10.1155/2018/4728645
spellingShingle Yingying Zhang
Siqi Zhao
Depei Wu
Xingmei Liu
Mingjun Shi
Yuanyuan Wang
Fan Zhang
Jing Ding
Ying Xiao
Bing Guo
MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy
Journal of Diabetes Research
title MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy
title_full MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy
title_fullStr MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy
title_full_unstemmed MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy
title_short MicroRNA-22 Promotes Renal Tubulointerstitial Fibrosis by Targeting PTEN and Suppressing Autophagy in Diabetic Nephropathy
title_sort microrna 22 promotes renal tubulointerstitial fibrosis by targeting pten and suppressing autophagy in diabetic nephropathy
url http://dx.doi.org/10.1155/2018/4728645
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