Seki Ekihiro, Brenner David A
Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, DAVIS, Suite D2099, Los Angeles, CA, 90048, USA.
School of Medicine, University of California San Diego, La Jolla, CA, USA.
J Hepatobiliary Pancreat Sci. 2015 Jul;22(7):512-8. doi: 10.1002/jhbp.245. Epub 2015 Apr 13.
Liver fibrosis occurs in response to any etiology of chronic liver injury including hepatitis B and C, alcohol consumption, fatty liver disease, cholestasis, and autoimmune hepatitis. Hepatic stellate cells (HSCs) are the primary source of activated myofibroblasts that produce extracellular matrix (ECM) in the liver. Various inflammatory and fibrogenic pathways contribute to the activation of HSCs. Recent studies also discovered that liver fibrosis is reversible and activated HSCs can revert to quiescent HSCs when causative agents are removed. Although the basic research for liver fibrosis has progressed remarkably, sensitive and specific biomarkers as non-invasive diagnostic tools, and effective anti-fibrotic agents have not been developed yet. This review highlights the recent advances in cellular and molecular mechanisms of liver fibrosis, especially focusing on origin of myofibroblasts, inflammatory signaling, autophagy, cellular senescence, HSC inactivation, angiogenesis, and reversibility of liver fibrosis.
肝纤维化可因任何慢性肝损伤病因引发,包括乙型和丙型肝炎、酒精摄入、脂肪性肝病、胆汁淤积以及自身免疫性肝炎。肝星状细胞(HSCs)是肝脏中产生细胞外基质(ECM)的活化肌成纤维细胞的主要来源。多种炎症和纤维化途径促使肝星状细胞活化。近期研究还发现,肝纤维化是可逆的,当致病因素去除后,活化的肝星状细胞可恢复为静止的肝星状细胞。尽管肝纤维化的基础研究取得了显著进展,但作为非侵入性诊断工具的敏感且特异的生物标志物以及有效的抗纤维化药物尚未研发出来。本综述重点介绍了肝纤维化细胞和分子机制的最新进展,尤其关注肌成纤维细胞的起源、炎症信号传导、自噬、细胞衰老、肝星状细胞失活、血管生成以及肝纤维化的可逆性。