Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepa1-6 cells and its relationship with collagen type IV.
OBJECTIVE
To investigate the regulation of activin receptor-interacting protein 2 (ARIP2) expression and its possible relationships with collagen type IV (collagen IV) in mouse hepatoma cell line Hepal-6 cells.


METHODS
The ARIP2 mRNA expression kinetics in Hepal-6 cells was detected by RT-PCR, and its regulation factors were analyzed by treatment with signal transduction activators such as phorbol 12-myristate 13-acetate (PMA), forskolin and A23187. After pcDNA3-ARIP2 was transfected into Hepal-6 cells, the effects of ARIP2 overexpression on activin type II receptor (ActRII) and collagen IV expression were evaluated.


RESULTS
The expression levels of ARIP2 mRNA in Hapel-6 cells were elevated in time-dependent manner 12 h after treatment with activin A and endotoxin LPS, but not changed evidently in the early stage of stimulation (2 or 4 h). The ARIP2 mRNA expression was increased after stimulated with signal transduction activators such as PMA and forskolin in Hepal-6 cells, whereas decreased after treatment with A23187 (25.3% +/- 5.7% vs 48.1% +/- 3.6%, P < 0.01). ARIP2 overexpression could remarkably suppress the expression of ActRIIA mRNA in dose-dependent manner, but has no effect on ActRIIB in Hepal-6 cells induced by activin A. Furthermore, we have found that overexpression of ARIP2 could inhibit collagen IV mRNA and protein expressions induced by activin A in Hapel-6 cells.


CONCLUSIONS
These findings suggest that ARIP2 expression can be influenced by various factors. ARIP2 may participate in the negative feedback regulation of signal transduction in the late stage by affecting the expression of ActRIIA and play an important role in regulation of development of liver fibrosis induced by activin.
Zhang
Hong-Jun
HJ
Department of Immunology, School of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin Province, China.
Tai
Gui-Xiang
GX
Zhou
Jing
J
Ma
Di
D
Liu
Zhong-Hui
ZH
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D028341:Activins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D024141:Collagen Type IV; D020536:Enzyme Activators; D007476:Ionophores; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; C457224:Synj2bp protein, mouse; C422405:activin A; C440499:lipopolysaccharide, Escherichia coli O111 B4; D028341:Activins; D005576:Colforsin; D000001:Calcimycin; D011493:Protein Kinase C; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium