Fibronectin expression is critical for liver fibrogenesis in vivo and in vitro.

Fibronectin expression is critical for liver fibrogenesis in vivo and in vitro.
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纤连蛋白表达对于体内和体外肝纤维化至关重要

DOI:
10.3892/mmr.2016.5673
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发表时间:
2016-10
影响因子:
3.4
通讯作者:
Yin CH
Yin CH
中科院分区:
医学4区
文献类型:
--
作者:
Liu XY;Liu RX;Hou F;Cui LJ;Li CY;Chi C;Yi E;Wen Y;Yin CH

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纤维连接蛋白(FN)表达增加在肝纤维化过程中具有重要作用。本研究探讨了四氯化碳(CCl 4)诱导的肝纤维化大鼠FN的表达。此外,通过将肝星状细胞(HSC)暴露于转化生长因子-β(TGF-β)(一种已知的HSC成肌纤维细胞转化诱导剂),研究了纤维发生的潜在机制。简单地说,通过腹膜内注射CCl 4建立肝纤维化大鼠模型。此外,HSC-T6细胞用增加剂量的重组TGF-β刺激24小时。CCl 4体内给药后肝纤维化逐渐增加。Western blotting和免疫组化结果显示,注射CCl 4后,纤维连接蛋白(FN)、TGF-β和α-平滑肌肌动蛋白(SMA)的表达均增加,在第8周达到最高水平。一旦CCl 4治疗终止,FN、TGF-β和α-SMA的表达水平逐渐下降至接近基线水平。Western blotting和定量聚合酶链反应显示,TGF-β刺激HSC后FN表达逐渐增加,12 h达最大值(P<0.01)。总之,这些研究结果表明,FN的表达是一个早期和渐进的事件,发生在肝纤维化在体内和体外。
Increased fibronectin (FN) expression has an important role during liver fibrosis. The present study examined FN expression in rats subjected to carbon tetrachloride (CCl4)-induced liver fibrosis. In addition, the potential mechanisms underlying fibrogenesis were investigated by exposing hepatic stellate cells (HSCs) to transforming growth factor-β (TGF-β), which is a known inducer of myofibroblastic transformation of HSCs. Briefly, a rat model of liver fibrosis was created by administering intraperitoneal injections of CCl4. Furthermore, HSC-T6 cells were stimulated with increasing doses of recombinant TGF-β over 24 h. Hepatic fibrosis gradually increased following CCl4 administration in vivo. Western blotting and immunohistochemistry demonstrated that fibronectin (FN), TGF-β and α-smooth muscle actin (SMA) expression was increased following CCl4 injection, and the maximum expression levels were observed at 8 weeks. Once CCl4 treatment had been terminated, the expression levels of FN, TGF-β and α-SMA progressively declined to near baseline levels. Western blotting and quantitative polymerase chain reaction demonstrated that FN expression was gradually increased in response to TGF-β-stimulation of HSCs; maximum expression was achieved 12 h post-treatment (P<0.01 vs. the baseline). In conclusion, these findings indicated that FN expression is an early and progressive event that occurs during liver fibrogenesis in vivo and in vitro.
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