Cargando…

Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT

Diabetic nephropathy is the leading cause of kidney fibrosis. Recently, altered expressed or dysfunction of some long non-coding RNAs (lncRNAs) has been linked to kidney fibrosis; however, the mechanisms of lncRNAs in kidney fibrosis remain unclear. We have shown that the DPP-4 inhibitor linagliptin...

Descripción completa

Detalles Bibliográficos
Autores principales: Shi, Sen, Song, Li, Yu, Hao, Feng, Songlin, He, Jianhua, Liu, Yong, He, Yanzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725869/
https://www.ncbi.nlm.nih.gov/pubmed/33324218
http://dx.doi.org/10.3389/fphar.2020.586895
_version_ 1783620788326236160
author Shi, Sen
Song, Li
Yu, Hao
Feng, Songlin
He, Jianhua
Liu, Yong
He, Yanzheng
author_facet Shi, Sen
Song, Li
Yu, Hao
Feng, Songlin
He, Jianhua
Liu, Yong
He, Yanzheng
author_sort Shi, Sen
collection PubMed
description Diabetic nephropathy is the leading cause of kidney fibrosis. Recently, altered expressed or dysfunction of some long non-coding RNAs (lncRNAs) has been linked to kidney fibrosis; however, the mechanisms of lncRNAs in kidney fibrosis remain unclear. We have shown that the DPP-4 inhibitor linagliptin can inhibit endothelial-mesenchymal transition (EndMT) and ameliorate diabetic kidney fibrosis associated with DPP-4 protein levels via the induction of miR-29. Here, we found that expression of the lncRNA H19 was significantly up-regulated in TGF-β2-induced fibrosis in human dermal microvascular endothelial cells (HMVECs) in vitro, and in kidney fibrosis of streptozotocin-induced diabetic CD-1 mice. We also detected up-regulated H19 expression and down-regulated miR-29a expression in the early and advanced mouse models of diabetic kidney fibrosis. H19 knockdown significantly attenuated kidney fibrosis in vitro and in vivo, which was associated with the inhibition of the EndMT-associated gene FSP-1. We also found that the up-regulation of H19 observed in fibrotic kidneys associated with the suppression of miR-29a in diabetic mice. H19, miR-29a, and EndMT contribute to a regulatory network involved in kidney fibrosis, and are associated with regulation of the TGF-β/SMAD3 singling pathway. This study indicates that inhibition of LncRNA H19 represents a novel anti-fibrotic treatment for diabetic kidney diseases.
format Online
Article
Text
id pubmed-7725869
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77258692020-12-14 Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT Shi, Sen Song, Li Yu, Hao Feng, Songlin He, Jianhua Liu, Yong He, Yanzheng Front Pharmacol Pharmacology Diabetic nephropathy is the leading cause of kidney fibrosis. Recently, altered expressed or dysfunction of some long non-coding RNAs (lncRNAs) has been linked to kidney fibrosis; however, the mechanisms of lncRNAs in kidney fibrosis remain unclear. We have shown that the DPP-4 inhibitor linagliptin can inhibit endothelial-mesenchymal transition (EndMT) and ameliorate diabetic kidney fibrosis associated with DPP-4 protein levels via the induction of miR-29. Here, we found that expression of the lncRNA H19 was significantly up-regulated in TGF-β2-induced fibrosis in human dermal microvascular endothelial cells (HMVECs) in vitro, and in kidney fibrosis of streptozotocin-induced diabetic CD-1 mice. We also detected up-regulated H19 expression and down-regulated miR-29a expression in the early and advanced mouse models of diabetic kidney fibrosis. H19 knockdown significantly attenuated kidney fibrosis in vitro and in vivo, which was associated with the inhibition of the EndMT-associated gene FSP-1. We also found that the up-regulation of H19 observed in fibrotic kidneys associated with the suppression of miR-29a in diabetic mice. H19, miR-29a, and EndMT contribute to a regulatory network involved in kidney fibrosis, and are associated with regulation of the TGF-β/SMAD3 singling pathway. This study indicates that inhibition of LncRNA H19 represents a novel anti-fibrotic treatment for diabetic kidney diseases. Frontiers Media S.A. 2020-11-26 /pmc/articles/PMC7725869/ /pubmed/33324218 http://dx.doi.org/10.3389/fphar.2020.586895 Text en Copyright © 2020 Shi, Song, Yu, Feng, He, Liu and He http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Shi, Sen
Song, Li
Yu, Hao
Feng, Songlin
He, Jianhua
Liu, Yong
He, Yanzheng
Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT
title Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT
title_full Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT
title_fullStr Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT
title_full_unstemmed Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT
title_short Knockdown of LncRNA-H19 Ameliorates Kidney Fibrosis in Diabetic Mice by Suppressing miR-29a-Mediated EndMT
title_sort knockdown of lncrna-h19 ameliorates kidney fibrosis in diabetic mice by suppressing mir-29a-mediated endmt
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725869/
https://www.ncbi.nlm.nih.gov/pubmed/33324218
http://dx.doi.org/10.3389/fphar.2020.586895
work_keys_str_mv AT shisen knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt
AT songli knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt
AT yuhao knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt
AT fengsonglin knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt
AT hejianhua knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt
AT liuyong knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt
AT heyanzheng knockdownoflncrnah19ameliorateskidneyfibrosisindiabeticmicebysuppressingmir29amediatedendmt