Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease
Background/Aims: Renal interstitial fibrosis (RIF) is a common feature that facilitates the progression of chronic kidney disease (CKD), and emerging lines of evidence suggest that microRNA-376b (miR-376b) is capable of promoting RIF. In this study, we examined collagen deposition in kidney tissues,...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Karger Publishers
2018-11-01
|
Series: | Kidney & Blood Pressure Research |
Subjects: | |
Online Access: | https://www.karger.com/Article/FullText/495394 |
id |
doaj-780561b67ce9478eaeaee6ac4f8be843 |
---|---|
record_format |
Article |
spelling |
doaj-780561b67ce9478eaeaee6ac4f8be8432020-11-25T03:45:05ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432018-11-014361749176410.1159/000495394495394Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney DiseaseShufen YangRizwanguli AbdullaChen LuLing ZhangBackground/Aims: Renal interstitial fibrosis (RIF) is a common feature that facilitates the progression of chronic kidney disease (CKD), and emerging lines of evidence suggest that microRNA-376b (miR-376b) is capable of promoting RIF. In this study, we examined collagen deposition in kidney tissues, the autophagy and mitochondrial reactive oxygen species (ROS) of macrophages, and the apoptosis of kidney fibroblasts (KFBs) after the promotion or suppression of endogenous miR-376b in cultured macrophages and renal fibroblasts obtained from mice with CKD. Methods: FVB/N mice were prepared to establish a CKD model. A target prediction program and luciferase activity determination were used to confirm that autophagy-related gene 5 (Atg5) was a direct target of miR-376b. Macrophages and KFBs were isolated after the treatment to study the mechanisms and functions of miR-376b in relation to Atg5 in CKD. The autophagy level was determined, and KFB proliferation and apoptosis were assessed through MTT and EdU assays and flow cytometry, respectively. Results: Atg5 was confirmed as a direct target of miR-376b. miR-376b and Atg5 exhibited high and low expression in kidney tissues from mice with CKD. The mice treated with a miR-376b inhibitor exhibited reduced collagen deposition, suppressed interstitial fibrosis, a higher level of autophagy, higher ROS production, enhanced apoptosis, and inhibited proliferation of KFBs, which suggested that the downregulation of miR-376b could exert beneficial effects on CKD through Atg5. Conclusion: miR-376b downregulation promotes macrophage autophagy to relieve RIF by negatively regulating Atg5 in mice with CKD. Thus, miR-376b might represent a potential focus of future investigations on treatments for CKD.https://www.karger.com/Article/FullText/495394microRNA-376bAutophagy-related gene 5MacrophagesKidney fibroblastsAutophagyRenal interstitial fibrosisChronic kidney disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shufen Yang Rizwanguli Abdulla Chen Lu Ling Zhang |
spellingShingle |
Shufen Yang Rizwanguli Abdulla Chen Lu Ling Zhang Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease Kidney & Blood Pressure Research microRNA-376b Autophagy-related gene 5 Macrophages Kidney fibroblasts Autophagy Renal interstitial fibrosis Chronic kidney disease |
author_facet |
Shufen Yang Rizwanguli Abdulla Chen Lu Ling Zhang |
author_sort |
Shufen Yang |
title |
Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease |
title_short |
Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease |
title_full |
Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease |
title_fullStr |
Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease |
title_full_unstemmed |
Inhibition of microRNA-376b Protects Against Renal Interstitial Fibrosis via Inducing Macrophage Autophagy by Upregulating Atg5 in Mice with Chronic Kidney Disease |
title_sort |
inhibition of microrna-376b protects against renal interstitial fibrosis via inducing macrophage autophagy by upregulating atg5 in mice with chronic kidney disease |
publisher |
Karger Publishers |
series |
Kidney & Blood Pressure Research |
issn |
1420-4096 1423-0143 |
publishDate |
2018-11-01 |
description |
Background/Aims: Renal interstitial fibrosis (RIF) is a common feature that facilitates the progression of chronic kidney disease (CKD), and emerging lines of evidence suggest that microRNA-376b (miR-376b) is capable of promoting RIF. In this study, we examined collagen deposition in kidney tissues, the autophagy and mitochondrial reactive oxygen species (ROS) of macrophages, and the apoptosis of kidney fibroblasts (KFBs) after the promotion or suppression of endogenous miR-376b in cultured macrophages and renal fibroblasts obtained from mice with CKD. Methods: FVB/N mice were prepared to establish a CKD model. A target prediction program and luciferase activity determination were used to confirm that autophagy-related gene 5 (Atg5) was a direct target of miR-376b. Macrophages and KFBs were isolated after the treatment to study the mechanisms and functions of miR-376b in relation to Atg5 in CKD. The autophagy level was determined, and KFB proliferation and apoptosis were assessed through MTT and EdU assays and flow cytometry, respectively. Results: Atg5 was confirmed as a direct target of miR-376b. miR-376b and Atg5 exhibited high and low expression in kidney tissues from mice with CKD. The mice treated with a miR-376b inhibitor exhibited reduced collagen deposition, suppressed interstitial fibrosis, a higher level of autophagy, higher ROS production, enhanced apoptosis, and inhibited proliferation of KFBs, which suggested that the downregulation of miR-376b could exert beneficial effects on CKD through Atg5. Conclusion: miR-376b downregulation promotes macrophage autophagy to relieve RIF by negatively regulating Atg5 in mice with CKD. Thus, miR-376b might represent a potential focus of future investigations on treatments for CKD. |
topic |
microRNA-376b Autophagy-related gene 5 Macrophages Kidney fibroblasts Autophagy Renal interstitial fibrosis Chronic kidney disease |
url |
https://www.karger.com/Article/FullText/495394 |
work_keys_str_mv |
AT shufenyang inhibitionofmicrorna376bprotectsagainstrenalinterstitialfibrosisviainducingmacrophageautophagybyupregulatingatg5inmicewithchronickidneydisease AT rizwanguliabdulla inhibitionofmicrorna376bprotectsagainstrenalinterstitialfibrosisviainducingmacrophageautophagybyupregulatingatg5inmicewithchronickidneydisease AT chenlu inhibitionofmicrorna376bprotectsagainstrenalinterstitialfibrosisviainducingmacrophageautophagybyupregulatingatg5inmicewithchronickidneydisease AT lingzhang inhibitionofmicrorna376bprotectsagainstrenalinterstitialfibrosisviainducingmacrophageautophagybyupregulatingatg5inmicewithchronickidneydisease |
_version_ |
1724511507178323968 |