Fausther Michel, Lavoie Elise G, Dranoff Jonathan A
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock AR 72205, USA.
Curr Pathobiol Rep. 2013 Sep;1(3):225-230. doi: 10.1007/s40139-013-0020-0.
The most common cause of liver failure is cirrhosis, due to progressive liver fibrosis and other architectural changes in the liver. Fibrosis occurs after liver injury or stress and results directly from an imbalance between the processes of extracellular matrix synthesis (fibrogenesis) and degradation (fibrolysis). Although research studies have identified several promising targets at the molecular level, current therapies to prevent and treat hepatic fibrosis in patients have only shown limited success. It is well established that liver myofibroblasts are the primary effector cells responsible for the extensive extracellular matrix accumulation and scar formation observed during hepatic fibrosis, in both clinical and experimental settings. Thus, as the major fibrogenic cells implicated in wound healing and tissue repair response, liver myofibroblasts could represent excellent targets for antifibrotic therapies. Still, the exact natures and identities of liver myofibroblasts precursors have yet to be resolved, and their relative contribution to hepatic fibrosis to be determined. The goal of this review is to examine the relative importance of liver myofibroblast precursors in the pathogenesis of liver fibrosis.
肝衰竭最常见的病因是肝硬化,它是由肝脏进行性纤维化和其他结构改变所致。纤维化在肝损伤或应激后发生,直接源于细胞外基质合成(纤维生成)与降解(纤维溶解)过程之间的失衡。尽管研究已在分子水平确定了几个有前景的靶点,但目前用于预防和治疗患者肝纤维化的疗法仅取得了有限的成功。众所周知,在临床和实验环境中,肝肌成纤维细胞是肝纤维化期间负责广泛细胞外基质积聚和瘢痕形成的主要效应细胞。因此,作为参与伤口愈合和组织修复反应的主要促纤维化细胞,肝肌成纤维细胞可能是抗纤维化疗法的理想靶点。然而,肝肌成纤维细胞前体的确切性质和身份尚未明确,它们对肝纤维化的相对贡献也有待确定。本综述的目的是探讨肝肌成纤维细胞前体在肝纤维化发病机制中的相对重要性。