Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Japan.
Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Japan.
FEBS Open Bio. 2022 Jun;12(6):1230-1240. doi: 10.1002/2211-5463.13405. Epub 2022 Apr 15.
Elevated interstitial fluid hydrostatic pressure is commonly observed in diseased livers. We herein examined the hypothesis that hydrostatic pressure induces hepatic stellate cells to acquire profibrotic properties under pathological conditions. Human hepatic stellate cells were exposed to 50 mmHg pressure for 24 h. Although we observed few changes of cell growth and morphology, PCR array data on the expression of fibrosis-associated genes suggested the acquisition of profibrotic properties. The exposure of hepatic stellate cells to 50 mmHg pressure for 24 h also significantly enhanced the expression of RhoA, ROCK1, α-SMA, TGF-β , p-MLC, and p-Smad2, and this was effectively attenuated by the ROCK inhibitor Y-27632. Our ex vivo experimental data suggest that elevated interstitial fluid hydrostatic pressure under pathological conditions may promote liver fibrosis by inducing acquisition of profibrotic properties of hepatic stellate cells through the RhoA/ROCK signaling pathway.
在病变的肝脏中，通常会观察到细胞间质流体静水压力升高。本研究旨在检验以下假说，即在病理条件下，静水压力会诱导肝星状细胞获得致纤维特性。将人肝星状细胞暴露于 50mmHg 压力下 24 小时。尽管我们观察到细胞生长和形态的变化很少，但与纤维化相关基因表达的 PCR 阵列数据表明获得了致纤维特性。将肝星状细胞暴露于 50mmHg 压力下 24 小时还显著增强了 RhoA、ROCK1、α-SMA、TGF-β、p-MLC 和 p-Smad2 的表达，而 RhoA/ROCK 信号通路抑制剂 Y-27632 可有效减弱这种表达。我们的离体实验数据表明，在病理条件下升高的细胞间质流体静水压力可能通过诱导肝星状细胞获得致纤维特性，从而促进肝纤维化，这一过程可能是通过 RhoA/ROCK 信号通路实现的。
