Rat hepatic stellate cells acquire retinoid responsiveness after activation in vitro by post-transcriptional regulation of retinoic acid receptor alpha gene expression
Rat hepatic stellate cells acquire retinoid responsiveness after activation in vitro by post-transcriptional regulation of retinoic acid receptor alpha gene expression
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DOI：
10.1016/j.abb.2007.06.024
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发表时间：
2007-09-15
影响因子：
3.9
通讯作者：
Senoo, Haruki
中科院分区：
文献类型：
--
作者：
Mezaki, Yoshihiro;Yoshikawa, Kiwamu;Senoo, Haruki
肝星状细胞（hepatic stellate cells，HSC）的活化是肝纤维化发生的关键过程，而维甲酸的丢失是HSC活化的显著特征。然而，类维生素A在肝纤维化中的作用尚不清楚。我们发现，RAR α，β和γ的mRNA水平在体外大鼠HSC激活过程中下降。然而，RAR α和β的蛋白水平在HSC活化期间增加。含有视黄酸反应元件的荧光素酶测定表明，HSC仅在体外活化后才对类维生素A有反应，并且这种反应至少部分由RAR α亚型介导。免疫细胞化学分析显示RAR α蛋白主要分布于胞浆中，呈斑点状。全反式维甲酸治疗强烈降低了细胞溶质RAR α蛋白水平。这些结果表明，大鼠HSC在体外活化后通过转录后上调RAR α基因表达而变得对类维生素A有反应。(C)2007年爱思唯尔公司All rights reserved.
Activation of hepatic stellate cells (HSCs) is a key process in liver fibrogenesis and retinoid loss is a remarkable feature of activated HSCs. However, roles of retinoids in liver fibrogenesis are obscure. We show that mRNA levels of RAR alpha, beta and gamma were decreased during rat HSC activation in vitro. However, protein levels of RAR alpha and beta were increased during HSC activation. A retinoic acid response element-containing luciferase assay indicated that HSCs became responsive to retinoids only after activation in vitro and that this response was mediated by, at least in part, RAR alpha subtype. Immunocytochemical analysis showed that RAR alpha proteins were mainly distributed in cytosol as many spots. All-trans retinoic acid treatment strongly lowered the cytosolic RAR alpha protein levels. These results indicate that rat HSCs become retinoid responsive after activation in vitro, through post-transcriptional up-regulation of RAR alpha gene expression. (C) 2007 Elsevier Inc. All rights reserved.