Transmembrane protein 88 attenuates liver fibrosis by promoting apoptosis and reversion of activated hepatic stellate cells.
Transmembrane protein 88 (Tmem88) is a crucial inhibitor for Wnt/β-catenin pathway in the development of myocardial cells. Due to the important role of β-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/β-catenin pathway, and promoted the apoptosis of activated HSCs by initiating Bcl-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.
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China. Electronic address: mengnanshuangpeng@163.com.
Shuang-Peng
SP
Cai
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China.
Xiao-Yu
XY
Cheng
Department of Pharmacy, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Pei-Jie
PJ
Chen
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China.
Xue-Yin
XY
Pan
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China.
Tao
T
Xu
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China.
Cheng
C
Huang
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China.
Xiao-Ming
XM
Meng
School of Pharmacy, Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
Jun
J
Li
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000502:physiology
C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D008565:Membrane Proteins; C555652:TMEM88 protein, human; C555653:TMEM88 protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
DNA metyltransferases (Dnmts); Hepatic stellate cells (HSCs); Liver fibrosis; Transmembrane protein 88 (Tmem88); Wnt/β-catenin