Embryonic liver fodrin involved in hepatic stellate cell activation and formation of regenerative nodule in liver cirrhosis

作者：Wang, Zhijun; Liu, Fang; Tu, Wei; Chang, Ying; Yao, Jinjian; Wu, Wei; Jiang, Xiang; He, Xingxing; Lin, Jusheng; Song, Yuhu^*

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2012, 16(1): 118-128.

DOI：10.1111/j.1582-4934.2011.01290.x

• b2-Spectrin
• hepatic stellate cell
• hepatic progenitor cell
• liver cirrhosis

Transforming growth factor (TGF) beta 1 plays a critical role in liver fibrosis. Previous studies demonstrated embryonic liver fodrin (ELF), a beta-spectrin was involved in TGF-beta/Smad signalling pathway as Smad3/4 adaptor. Here we investigate the role of ELF in pathogenesis of liver cirrhosis. In carbon tetrachloride (CCl4)-induced mice model of liver cirrhosis, ELF is up-regulated in activated hepatic stellate cells (HSCs), and down-regulated in regenerative hepatocytes of cirrhotic nodules. In activated HSCs in vitro, reduction of ELF expression mediated by siRNA leads to the inhibition of HSC activation and procollagen I expression. BrdU assay demonstrates that down-regulation of ELF expression does not inhibit proliferation of activated HSCs in vitro. Immunostaining of cytokeratin 19 and Ki67 indicates that regenerative hepatocytes in cirrhotic liver are derived from hepatic progenitor cells (HPC). Further study reveals that HPC expansion occurs as an initial phase, before the reduction of ELF expression in regenerative hepatocytes. Regenerative hepatocytes in cirrhotic liver show the change in proliferative activity and expression pattern of proteins involved in G1/S transition, which suggests the deregulation of cell cycle in regenerative hepatocytes. Finally, we find that ELF participates in TGF-beta/Smad signal in activated HSCs and hepatocytes through regulating the localization of Smad3/4. These data reveal that ELF is involved in HSC activation and the formation of regenerative nodules derived from HPC in cirrhotic liver.

• 出版日期2012-1
• 单位华中科技大学