State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Matrix Biol. 2018 Mar;66:81-92. doi: 10.1016/j.matbio.2017.09.004. Epub 2017 Sep 28.
Periostin (Postn) is a crucial extracellular remodeling factor that has been implicated in the pathogenesis of hepatic inflammation, fibrosis, non-alcoholic fatty liver disease and liver cancer. However, the role of Postn in liver regeneration remains unclear. Here, we demonstrate that Postn mRNA and protein levels are significantly upregulated in the mice after 2/3 partial hepatectomy (PHx). Compared with wild-type mice, Postn-deficient mice exhibit lower liver/body weight ratio and less Ki67-positive cells at days 2, 8 and 14 after PHx. Macrophage infiltration and the levels of TNF-α, IL-6 and HGF in the livers of Postn-deficient mice are significantly decreased compared with wild-type mice one day after PHx. In addition, overexpression of Postn leads to higher liver/body weight ratio and more Ki67-positive cells in the livers of mice and promotes hepatocyte proliferation in vitro. Moreover, liver sinusoidal endothelial cells, biliary epithelial cells and hepatocytes can express Postn after PHx, and Postn deficiency impairs angiogenesis during liver regeneration. Our findings indicate that Postn deficiency impairs liver regeneration in mice after PHx and Postn might be a novel promoter for liver regeneration.
纤连蛋白(Postn)是一种重要的细胞外重塑因子,与肝炎症、纤维化、非酒精性脂肪性肝病和肝癌的发病机制有关。然而,Postn 在肝再生中的作用尚不清楚。本研究显示,在 2/3 部分肝切除(PHx)后,小鼠的 Postn mRNA 和蛋白水平显著上调。与野生型小鼠相比,Postn 缺陷型小鼠在 PHx 后第 2、8 和 14 天的肝/体重比更低,Ki67 阳性细胞更少。PHx 后 1 天,Postn 缺陷型小鼠的肝巨噬细胞浸润和 TNF-α、IL-6 和 HGF 水平明显低于野生型小鼠。此外,过表达 Postn 可使小鼠肝脏的肝/体重比更高,Ki67 阳性细胞更多,并促进体外肝细胞增殖。此外,PHx 后肝窦内皮细胞、胆管上皮细胞和肝细胞均可表达 Postn,Postn 缺陷可损害肝再生过程中的血管生成。本研究结果表明,Postn 缺陷可损害 PHx 后小鼠的肝再生,Postn 可能是肝再生的新促进剂。