Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction.
Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1) is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiprolife...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4713170?pdf=render |
_version_ | 1811231000508760064 |
---|---|
author | Xiao Chen Shi-Yao Wei Jian-Si Li Qing-Fang Zhang Yu-Xiao Wang Shi-Lei Zhao Jing Yu Chang Wang Ying Qin Qiu-Ju Wei Gui-Xiang Lv Bing Li |
author_facet | Xiao Chen Shi-Yao Wei Jian-Si Li Qing-Fang Zhang Yu-Xiao Wang Shi-Lei Zhao Jing Yu Chang Wang Ying Qin Qiu-Ju Wei Gui-Xiang Lv Bing Li |
author_sort | Xiao Chen |
collection | DOAJ |
description | Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1) is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiproliferative, and immunomodulatory effects. However, the mechanisms of HO-1 prevention in renal interstitial fibrosis remain unknown. In this study, HO-1 transgenic (TG) mice were employed to investigate the effect of HO-1 on renal fibrosis using a unilateral ureter obstruction (UUO) model and to explore the potential mechanisms. We found that HO-1 was adaptively upregulated in kidneys of both TG and wild type (WT) mice after UUO. The levels of HO-1 mRNA and protein were increased in TG mice compared with WT mice under normal conditions. HO-1 expression was further enhanced after UUO and remained high during the entire experimental process. Renal interstitial fibrosis in the TG group was significantly attenuated compared with that in the WT group after UUO. Moreover, overexpression of HO-1 inhibited the loss of peritubular capillaries. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by HO-1 overexpression. Furthermore, HO-1 restrained tubulointerstitial infiltration of macrophages and regulated the secretion of inflammatory cytokines in UUO mice. We also found that high expression of HO-1 inhibited reactivation of Wnt/β-catenin signaling, which could play a crucial role in attenuating renal fibrosis. In conclusion, these data suggest that HO-1 prevents renal tubulointerstitial fibrosis possibly by regulating the inflammatory response and Wnt/β-catenin signaling. This study provides evidence that augmentation of HO-1 levels may be a therapeutic strategy against renal interstitial fibrosis. |
first_indexed | 2024-04-12T10:37:48Z |
format | Article |
id | doaj.art-0c8e7f1e2e67471fbd8e46a01065392f |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-12T10:37:48Z |
publishDate | 2016-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-0c8e7f1e2e67471fbd8e46a01065392f2022-12-22T03:36:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014708410.1371/journal.pone.0147084Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction.Xiao ChenShi-Yao WeiJian-Si LiQing-Fang ZhangYu-Xiao WangShi-Lei ZhaoJing YuChang WangYing QinQiu-Ju WeiGui-Xiang LvBing LiRenal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1) is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiproliferative, and immunomodulatory effects. However, the mechanisms of HO-1 prevention in renal interstitial fibrosis remain unknown. In this study, HO-1 transgenic (TG) mice were employed to investigate the effect of HO-1 on renal fibrosis using a unilateral ureter obstruction (UUO) model and to explore the potential mechanisms. We found that HO-1 was adaptively upregulated in kidneys of both TG and wild type (WT) mice after UUO. The levels of HO-1 mRNA and protein were increased in TG mice compared with WT mice under normal conditions. HO-1 expression was further enhanced after UUO and remained high during the entire experimental process. Renal interstitial fibrosis in the TG group was significantly attenuated compared with that in the WT group after UUO. Moreover, overexpression of HO-1 inhibited the loss of peritubular capillaries. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by HO-1 overexpression. Furthermore, HO-1 restrained tubulointerstitial infiltration of macrophages and regulated the secretion of inflammatory cytokines in UUO mice. We also found that high expression of HO-1 inhibited reactivation of Wnt/β-catenin signaling, which could play a crucial role in attenuating renal fibrosis. In conclusion, these data suggest that HO-1 prevents renal tubulointerstitial fibrosis possibly by regulating the inflammatory response and Wnt/β-catenin signaling. This study provides evidence that augmentation of HO-1 levels may be a therapeutic strategy against renal interstitial fibrosis.http://europepmc.org/articles/PMC4713170?pdf=render |
spellingShingle | Xiao Chen Shi-Yao Wei Jian-Si Li Qing-Fang Zhang Yu-Xiao Wang Shi-Lei Zhao Jing Yu Chang Wang Ying Qin Qiu-Ju Wei Gui-Xiang Lv Bing Li Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction. PLoS ONE |
title | Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction. |
title_full | Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction. |
title_fullStr | Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction. |
title_full_unstemmed | Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction. |
title_short | Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction. |
title_sort | overexpression of heme oxygenase 1 prevents renal interstitial inflammation and fibrosis induced by unilateral ureter obstruction |
url | http://europepmc.org/articles/PMC4713170?pdf=render |
work_keys_str_mv | AT xiaochen overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT shiyaowei overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT jiansili overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT qingfangzhang overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT yuxiaowang overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT shileizhao overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT jingyu overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT changwang overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT yingqin overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT qiujuwei overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT guixianglv overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction AT bingli overexpressionofhemeoxygenase1preventsrenalinterstitialinflammationandfibrosisinducedbyunilateralureterobstruction |