Zhang Hong-Jun, Tai Gui-Xiang, Zhou Jing, Ma Di, Liu Zhong-Hui
Department of Immunology, School of Basic Medical Sciences, Jilin University, Changchun 130021, Jilin Province, China.
World J Gastroenterol. 2007 Nov 7;13(41):5501-5. doi: 10.3748/wjg.v13.i41.5501.
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.
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.
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.
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.
研究激活素受体相互作用蛋白2（ARIP2）在小鼠肝癌细胞系Hepal-6细胞中的表达调控及其与IV型胶原（胶原IV）的可能关系。
采用逆转录聚合酶链反应（RT-PCR）检测Hepal-6细胞中ARIP2 mRNA的表达动力学，并用佛波酯12-肉豆蔻酸13-乙酸酯（PMA）、福斯高林和A23187等信号转导激活剂处理分析其调控因子。将pcDNA3-ARIP2转染入Hepal-6细胞后，评估ARIP2过表达对激活素II型受体（ActRII）和胶原IV表达的影响。
用激活素A和内毒素LPS处理12小时后，Hapel-6细胞中ARIP2 mRNA的表达水平呈时间依赖性升高，但在刺激早期（2或4小时）无明显变化。用PMA和福斯高林等信号转导激活剂刺激后，Hepal-6细胞中ARIP2 mRNA表达增加，而用A23187处理后表达降低（25.3%±5.7%对48.1%±3.6%，P<0.01）。ARIP2过表达能以剂量依赖性方式显著抑制激活素A诱导的Hepal-6细胞中ActRIIA mRNA的表达，但对ActRIIB无影响。此外，我们发现ARIP2过表达能抑制激活素A诱导的Hapel-6细胞中胶原IV mRNA和蛋白的表达。
这些发现表明ARIP2的表达可受多种因素影响。ARIP2可能通过影响ActRIIA的表达参与后期信号转导的负反馈调节，并在激活素诱导的肝纤维化发展调控中起重要作用。
