Lin Nan, Tang Zhaofeng, Deng Meihai, Zhong Yuesi, Lin Jizong, Yang Xuhui, Xiang Peng, Xu Ruiyun
Division of Hepatology, The Third Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou City 510630, Guangdong Province, China.
Biochem Biophys Res Commun. 2008 Jul 18;372(1):260-5. doi: 10.1016/j.bbrc.2008.05.029. Epub 2008 May 16.
During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis.
在肝损伤期间，骨髓间充质干细胞（MSCs）可迁移并分化为肝细胞。肝星状细胞（SCs）激活是肝纤维化发展中的关键事件。因此，我们推测SCs可能通过旁分泌信号通路在调节MSCs增殖和分化中发挥重要作用。我们证明MSCs和SCs均表达刺猬（Hh）信号通路成分，包括其配体、受体和靶基因。SCs与MSCs的Transwell共培养显示SCs产生音猬因子（Shh），其增强了MSCs的增殖和分化。这些发现表明SCs在体外通过Hh信号通路间接调节MSCs的活性，并为移植MSCs治疗肝纤维化的机制提供了合理的解释。
