Liu Zhiyong, Yi Jian, Ye Rong, Liu Jianping, Duan Qing, Xiao Junqi, Liu Fengen
Department of Vascular and Breast Surgery, The First Affiliated Hospital of Gannan Medical University 23 Qingnian Road, Ganzhou 341000, China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):3994-4000. eCollection 2015.
Activation of hepatic stellate cells (HSCs) into collagen producing myofibroblasts is critical for pathogenesis of liver fibrosis. Transforming growth factor-β1 (TGF-β1) is one of the main profibrogenic mediators for HSC transdifferentiation. Recent studies have shown effect of microRNAs (miRNAs) on regulating TGF-β1-induced HSC activation during liver fibrosis. Here, we aimed to explore the roles of miR-144 and miR-200c in human liver fibrosis.
Expression of TGF-β1 was detected in 42 fibrotic and 18 normal human liver tissues by quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry, and its correlation with α-smooth muscle actin (α-SMA) was calculated. miR-144 and miR-200c expression level in fibrotic liver tissues were also detected by qRT-PCR. The correlation of TGF-β1 expression with miR-200c and miR-144 in the fibrotic liver was analyzed.
The results showed that TGF-β1 expression was much higher in fibrotic liver than that in normal liver tissues (P<0.05). TGF-β1 protein high expressing liver fibrosis showed α-SMA positive cells in the liver parenchyma indicating activated HSCs. Expression of TGF-β1 in fibrotic liver was significantly correlated with α-SMA expression (R=0.633, P<0.001). Furthermore, miR-144 was less expressed in liver fibrosis (P<0.05) and was significantly correlated with expression of TGF-β1 in fibrotic liver tissues (R=-0.442, P<0.01). However, miR-200c did not show significant difference between normal and fibrotic liver (P=0.48) and correlation with TGF-β1 expression (R=0.106, P=0.51).
All the results indicate that miR-144 can be a novel regulator of TGF-β1-induced HSC activation during liver fibrosis.
肝星状细胞（HSCs）激活成为产生胶原蛋白的肌成纤维细胞对于肝纤维化的发病机制至关重要。转化生长因子-β1（TGF-β1）是HSC转分化的主要促纤维化介质之一。最近的研究表明，微小RNA（miRNAs）在肝纤维化过程中对调节TGF-β1诱导的HSC激活具有作用。在此，我们旨在探讨miR-144和miR-200c在人类肝纤维化中的作用。
通过定量实时聚合酶链反应（qRT-PCR）和免疫组织化学检测42例纤维化和18例正常人类肝组织中TGF-β1的表达，并计算其与α-平滑肌肌动蛋白（α-SMA）的相关性。还通过qRT-PCR检测纤维化肝组织中miR-144和miR-200c的表达水平。分析纤维化肝中TGF-β1表达与miR-200c和miR-144的相关性。
结果显示，纤维化肝中TGF-β1的表达远高于正常肝组织（P<0.05）。TGF-β1蛋白高表达的肝纤维化在肝实质中显示α-SMA阳性细胞，表明HSCs被激活。纤维化肝中TGF-β1的表达与α-SMA表达显著相关（R=0.633，P<0.001）。此外，miR-144在肝纤维化中表达较低（P<0.05），并且与纤维化肝组织中TGF-β1的表达显著相关（R=-0.442，P<0.01）。然而，miR-200c在正常肝和纤维化肝之间未显示出显著差异（P=0.48），且与TGF-β1表达无相关性（R=0.106，P=0.51）。
所有结果表明，miR-144可能是肝纤维化过程中TGF-β1诱导的HSC激活的新型调节因子。
