NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats.
Liver fibrosis is a worldwide clinical issue. It has been well established that activated hepatic stellate cells (HSCs) are responsible for excessive extracellular matrix (ECM) deposition in chronically damaged livers. The identification of key elements that control HSCs activation will help to furt...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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Series: | PLoS ONE |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110735/pdf/?tool=EBI |
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author | Jiandong Yang Jin Zheng Lin Wu Ming Shi Hongtao Zhang Xing Wang Ning Xia Desheng Wang Xinping Liu Libo Yao Yan Li Kefeng Dou |
author_facet | Jiandong Yang Jin Zheng Lin Wu Ming Shi Hongtao Zhang Xing Wang Ning Xia Desheng Wang Xinping Liu Libo Yao Yan Li Kefeng Dou |
author_sort | Jiandong Yang |
collection | DOAJ |
description | Liver fibrosis is a worldwide clinical issue. It has been well established that activated hepatic stellate cells (HSCs) are responsible for excessive extracellular matrix (ECM) deposition in chronically damaged livers. The identification of key elements that control HSCs activation will help to further our understanding of liver fibrosis and improve the outcome of clinical treatment. This study demonstrates that N-Myc downstream-regulated gene 2 (NDRG2) is a potential regulator of liver fibrosis as NDRG2 mRNA and protein levels were reduced during HSCs activation. In addition, enhanced NDRG2 expression reduced Smad3 transcription and phosphorylation, which inhibited HSCs activation by blocking the TGF-β1 signal. Moreover, NDRG2 contributed to an increase in the ratio of matrix metalloproteinase 2 (MMP2) to tissue inhibitor of matrix metalloproteinase 2 (TIMP2), which may facilitate the degradation of the ECM. In dimethylnitrosamine (DMN)-induced fibrotic rat livers, adenovirus-mediated NDRG2 overexpression resulted in decreased ECM deposition and improved liver function compared with controls. In conclusion, the present findings indicate that the modulation of NDRG2 is a promising strategy for the treatment of liver fibrosis. |
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id | doaj.art-e1c3f31c3d8d4426b6c447a7cdb7943a |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
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publishDate | 2011-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-e1c3f31c3d8d4426b6c447a7cdb7943a2022-12-21T21:27:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2771010.1371/journal.pone.0027710NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats.Jiandong YangJin ZhengLin WuMing ShiHongtao ZhangXing WangNing XiaDesheng WangXinping LiuLibo YaoYan LiKefeng DouLiver fibrosis is a worldwide clinical issue. It has been well established that activated hepatic stellate cells (HSCs) are responsible for excessive extracellular matrix (ECM) deposition in chronically damaged livers. The identification of key elements that control HSCs activation will help to further our understanding of liver fibrosis and improve the outcome of clinical treatment. This study demonstrates that N-Myc downstream-regulated gene 2 (NDRG2) is a potential regulator of liver fibrosis as NDRG2 mRNA and protein levels were reduced during HSCs activation. In addition, enhanced NDRG2 expression reduced Smad3 transcription and phosphorylation, which inhibited HSCs activation by blocking the TGF-β1 signal. Moreover, NDRG2 contributed to an increase in the ratio of matrix metalloproteinase 2 (MMP2) to tissue inhibitor of matrix metalloproteinase 2 (TIMP2), which may facilitate the degradation of the ECM. In dimethylnitrosamine (DMN)-induced fibrotic rat livers, adenovirus-mediated NDRG2 overexpression resulted in decreased ECM deposition and improved liver function compared with controls. In conclusion, the present findings indicate that the modulation of NDRG2 is a promising strategy for the treatment of liver fibrosis.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110735/pdf/?tool=EBI |
spellingShingle | Jiandong Yang Jin Zheng Lin Wu Ming Shi Hongtao Zhang Xing Wang Ning Xia Desheng Wang Xinping Liu Libo Yao Yan Li Kefeng Dou NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. PLoS ONE |
title | NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. |
title_full | NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. |
title_fullStr | NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. |
title_full_unstemmed | NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. |
title_short | NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats. |
title_sort | ndrg2 ameliorates hepatic fibrosis by inhibiting the tgf β1 smad pathway and altering the mmp2 timp2 ratio in rats |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22110735/pdf/?tool=EBI |
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