title: NDRG2 ameliorates hepatic fibrosis by inhibiting the TGF-β1/Smad pathway and altering the MMP2/TIMP2 ratio in rats.
abstract: 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.
authors: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Jiandong
authors: J
authors: Yang
authors: Jin
authors: J
authors: Zheng
authors: Lin
authors: L
authors: Wu
authors: Ming
authors: M
authors: Shi
authors: Hongtao
authors: H
authors: Zhang
authors: Xing
authors: X
authors: Wang
authors: Ning
authors: N
authors: Xia
authors: Desheng
authors: D
authors: Wang
authors: Xinping
authors: X
authors: Liu
authors: Libo
authors: L
authors: Yao
authors: Yan
authors: Y
authors: Li
authors: Kefeng
authors: K
authors: Dou
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C466228:NDRG2 protein, human; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D004128:Dimethylnitrosamine