Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was inc...

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Main Authors: Ning Yan, Li Wen, Rui Peng, Hongmei Li, Handeng Liu, Huimin Peng, Yan Sun, Tianhui Wu, Lei Chen, Qingrui Duan, Yixuan Sun, Qin Zhou, Lijiang Wei, Zheng Zhang
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2016/8738760
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author Ning Yan
Li Wen
Rui Peng
Hongmei Li
Handeng Liu
Huimin Peng
Yan Sun
Tianhui Wu
Lei Chen
Qingrui Duan
Yixuan Sun
Qin Zhou
Lijiang Wei
Zheng Zhang
author_facet Ning Yan
Li Wen
Rui Peng
Hongmei Li
Handeng Liu
Huimin Peng
Yan Sun
Tianhui Wu
Lei Chen
Qingrui Duan
Yixuan Sun
Qin Zhou
Lijiang Wei
Zheng Zhang
author_sort Ning Yan
collection DOAJ
description Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.
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spelling doaj-art-a7531f9b5b0840fa81e04976e46b7d3f2025-08-20T02:20:56ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/87387608738760Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic NephropathyNing Yan0Li Wen1Rui Peng2Hongmei Li3Handeng Liu4Huimin Peng5Yan Sun6Tianhui Wu7Lei Chen8Qingrui Duan9Yixuan Sun10Qin Zhou11Lijiang Wei12Zheng Zhang13Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaMolecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaDepartment of Bioinformatics, Chongqing Medical University, Chongqing 400016, ChinaChongqing Red Cross Hospital, Chongqing 400016, ChinaMolecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaMolecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaMolecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaMolecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaThe Second Clinical College, Chongqing Medical University, Chongqing 400016, ChinaThe Second Clinical College, Chongqing Medical University, Chongqing 400016, ChinaThe Second Clinical College, Chongqing Medical University, Chongqing 400016, ChinaThe Second Clinical College, Chongqing Medical University, Chongqing 400016, ChinaThe First Clinical College, Chongqing Medical University, Chongqing 400016, ChinaMolecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, ChinaDiabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.http://dx.doi.org/10.1155/2016/8738760
spellingShingle Ning Yan
Li Wen
Rui Peng
Hongmei Li
Handeng Liu
Huimin Peng
Yan Sun
Tianhui Wu
Lei Chen
Qingrui Duan
Yixuan Sun
Qin Zhou
Lijiang Wei
Zheng Zhang
Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
Journal of Diabetes Research
title Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
title_full Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
title_fullStr Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
title_full_unstemmed Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
title_short Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy
title_sort naringenin ameliorated kidney injury through let 7a tgfbr1 signaling in diabetic nephropathy
url http://dx.doi.org/10.1155/2016/8738760
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