Transmembrane protein 88 attenuates liver fibrosis by promoting apoptosis and reversion of activated hepatic stellate cells

被引：26

作者：

Cai, Shuang-Peng ^{[1
,2
]}

Cheng, Xiao-Yu ^{[1
,2
]}

Chen, Pei-Jie ^{[3
]}

Pan, Xue-Yin ^{[1
,2
]}

Xu, Tao ^{[1
,2
]}

Huang, Cheng ^{[1
,2
]}

Meng, Xiao-Ming ^{[1
,2
]}

Li, Jun ^{[1
,2
]}

机构：

[1] Anhui Med Univ, Sch Pharm, Lab Bioact Nat Prod, Hefei 230032, Peoples R China

[2] Anhui Med Univ, ILD, Hefei 230032, Peoples R China

[3] Anhui Med Univ, Affiliated Hosp 4, Dept Pharm, Hefei 230022, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2016年 / 80卷

基金：

美国国家科学基金会;

关键词：

Liver fibrosis; Transmembrane protein 88 (Tmem88); Hepatic stellate cells (HSCs); DNA metyltransferases (Dnmts); Wnt/beta-catenin; WNT SIGNALING PATHWAY; BETA-CATENIN; IDENTIFICATION;

D O I：

10.1016/j.molimm.2016.11.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transmembrane protein 88 (Tmem88) is a crucial inhibitor for Wnt/beta-catenin pathway in the development of myocardial cells. Due to the important role of beta-catenin in the activation and proliferation of hepatic stellate cells (HSCs), it is necessary to investigate the function of Tmem88 in HSCs. In this study, we found that Tmem88 expression was decreased in the human liver fibrotic tissues, primary HSCs from fibrotic mice and activated HSC-T6 cells. Functionally, Tmem88 could inhibit HSCs activation and proliferation by blocking Wnt/beta-catenin pathway, and promoted the apoptosis of activated HSCs by initiating Bc1-2/Bax/Caspase3 pathway. Moreover, the level of DNA metyltransferase 3a (Dnmt3a) was upregulated in activated HSCs, and siRNA-mediated Dnmt3a silencing led to Tmem88 restoration. These results indicated that Tmem88 played an important role in HSCs activation, proliferation and apoptosis, and Tmem88 expression might be modulated by Dnmt3a. (C)2016 Published by Elsevier Ltd.

引用

页码：58 / 67

页数：10

共 29 条

[1] Epigenetic therapy as a novel approach in hepatocellular carcinoma [J].

Anestopoulos, Ioannis ;

Voulgaridou, Georgia Persephoni ;

Georgakilas, Alexandros G. ;

Franco, Rodrigo ;

Pappa, Aglaia ;

Panayiotidis, Mihalis I. .

PHARMACOLOGY & THERAPEUTICS, 2015, 145 :103-119

[2] Liver fibrosis [J].

Bataller, R ;

Brenner, DA .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) :209-218

[3] The basement membrane component of biologic scaffolds derived from extracellular matrix [J].

Brown, B ;

Lindberg, K ;

Reing, J ;

Stolz, DB ;

Badylak, SF .

TISSUE ENGINEERING, 2006, 12 (03) :519-526

[4] Programming of DNA Methylation Patterns [J].

Cedar, Howard ;

Bergman, Yehudit .

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 81, 2012, 81 :97-117

[5] PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells [J].

Chen, Pei-Jie ;

Cai, Shuang-Peng ;

Yang, Yang ;

Li, Wan-Xia ;

Huang, Cheng ;

Meng, Xiao-Ming ;

Li, Jun .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2016, 292 :8-18

[6] Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis [J].

Cheng, Jason H. ;

She, Hongyun ;

Han, Yuan-Ping ;

Wang, Jiaohong ;

Xiong, Shigang ;

Asahina, Kinji ;

Tsukamoto, Hidekazu .

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2008, 294 (01) :G39-G49

[7] In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-α [J].

Connolly, Michael K. ;

Bedrosian, Andrea S. ;

Clair, Jon Mallen-St. ;

Mitchell, Aaron P. ;

Ibrahim, Junaid ;

Stroud, Andrea ;

Pachter, H. Leon ;

Bar-Sagi, Dafna ;

Frey, Alan B. ;

Miller, George .

JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (11) :3213-3225

[8] Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver [J].

Friedman, Scott L. .

PHYSIOLOGICAL REVIEWS, 2008, 88 (01) :125-172

[9] β-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/β-catenin signaling inhibits hepatic stellate cell activation [J].

Ge, Wen-Song ;

Wang, Yao-Jun ;

Wu, Jian-Xin ;

Fan, Jian-Gao ;

Chen, Ying-Wei ;

Zhu, Liang .

MOLECULAR MEDICINE REPORTS, 2014, 9 (06) :2145-2151

[10] Wnt/β-Catenin Signaling: a Promising New Target for Fibrosis Diseases [J].

Guo, Y. ;

Xiao, L. ;

Sun, L. ;

Liu, F. .

PHYSIOLOGICAL RESEARCH, 2012, 61 (04) :337-346

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