门静脉成纤维细胞有望成为可再生肌成纤维细胞的新来源

摘要/Abstract

摘要： 间充质细胞在组织稳态和伤口愈合中扮演着重要角色。在肝脏中,间充质细胞包括位于肝窦的肝星状细胞(HSCs)、位于门静脉和中央静脉周围的血管平滑肌细胞(VSMCs)和成纤维细胞。肌成纤维细胞与平滑肌细胞有共同的基因表达谱,通过产生基质成为纤维化疾病的效应细胞。HSCs因具有向肌成纤维细胞分化的能力而受到广泛研究,被确定为肝纤维化中肌成纤维细胞的主要来源。目前的研究表明其他肝脏间充质细胞,特别是门静脉间充质细胞也能产生肌成纤维细胞。然而关于门静脉间充质细胞的特性、组成、功能,以及它们如何促进纤维化,目前所知甚少,一个主要的限制是缺乏能够分离或在体内示踪门静脉间充质细胞的标志物。本文将结合门静脉间充质细胞的最新研究进展对门静脉成纤维细胞的特性作一阐述,介绍一种具有间充质干细胞特征(PMSCs)并可以生成肌成纤维细胞的门静脉成纤维细胞亚群,为后续研究这群细胞在小鼠和人类肝纤维化过程中的作用奠定基础。

关键词: 肝脏间充质细胞, 门静脉成纤维细胞, 肌成纤维细胞, 再生, 肝纤维化

马鸿倩, 鄢和新. 门静脉成纤维细胞有望成为可再生肌成纤维细胞的新来源[J]. 肝脏, 2022, 27(12): 1265-1267.

参考文献

[1] Pinzani M. Liver fibrosis. Springer Semin Immunopathol,1999,21:475-490.
[2] Asahina K, Zhou B, Pu WT, et al. Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver. Hepatology,2011,53:983-995.
[3] Enzan H, Himeno H, Hiroi M, et al. Development of hepatic sinusoidal structure with special reference to the Ito cells. Microsc Res Tech,1997,39:336-349.
[4] Friedman SL, Roll FJ, Boyles J, et al. Hepatic lipocytes: the principal collagen-producing cells of normal rat liver. Proc Natl Acad Sci U S A,1985,82:8681-8685.
[5] Filliol A, Saito Y, Nair A, et al. Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis. Nature,2022,610:356-365.
[6] Bosselut N, Housset C, Marcelo P, et al. Distinct proteomic features of two fibrogenic liver cell populations: hepatic stellate cells and portal myofibroblasts. Proteomics, 2010,10:1017-1028.
[7] Lemoinne S, Cadoret A, Rautou PE, et al. Portal myofibroblasts promote vascular remodeling underlying cirrhosis formation through the release of microparticles. Hepatology,2015,61:1041-1055.
[8] Lua I, Li Y, Zagory JA, et al. Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers. J Hepatol,2016,64:1137-1146.
[9] Nishio T, Hu R, Koyama Y, et al. Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice. J Hepatol,2019,71:573-585.
[10] Schaffner F, Barka T, Popper H. Hepatic mesenchymal cell reaction in liver disease. Exp Mol Pathol,1963,2:419-441.
[11] Kinnman N, Housset C. Peribiliary myofibroblasts in biliary type liver fibrosis. Front Biosci, 2002,7:d496-503.
[12] Dranoff JA, Wells RG. Portal fibroblasts: Underappreciated mediators of biliary fibrosis. Hepatology,2010,51:1438-1444.
[13] Lei L, Bruneau A, El Mourabit H, et al. Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis. Hepatology,2022,76:1360-1375.
[14] Chen W, Teschendorff AE. Estimating Differentiation Potency of Single Cells Using Single-Cell Entropy (SCENT). Methods Mol Biol,2019,1935:125-139.
[15] Fuji H, Miller G, Nishio T, et al. The role of Mesothelin signaling in Portal Fibroblasts in the pathogenesis of cholestatic liver fibrosis. Front Mol Biosci,2021,8:790032.
[16] Trussoni CE, O’Hara SP, LaRusso NF. Cellular senescence in the cholangiopathies: a driver of immunopathology and a novel therapeutic target. Semin Immunopathol, 2022,44:527-544.
[17] Guicciardi ME, Trussoni CE, LaRusso NF, et al. The Spectrum of Reactive Cholangiocytes in Primary Sclerosing Cholangitis. Hepatology,2020,71:741-748.