Hepatic stellate cells in physiology and pathology.
Hepatic stellate cells in physiology and pathology.
复制标题
肝星状细胞的生理与病理。
DOI：
10.1113/jp281061
复制
发表时间：
2022-04
影响因子：
5.5
通讯作者：
McCommis, Kyle S.
中科院分区：
文献类型：
--
作者：
Kamm, Dakota R.;McCommis, Kyle S.
Hepatic stellate cells (HSCs) comprise a minor cell population in the liver but serve numerous critical functions in the normal liver and in response to injury. HSCs are primarily known for their activation upon liver injury and producing the collagen-rich extracellular matrix in liver fibrosis. In the absence of liver injury, HSCs reside in a quiescent state, in which their main function appears to be storage of retinoids, or vitamin A containing metabolites. Less appreciated functions of HSCs include amplifying the hepatic inflammatory response and expressing growth factors that are critical for liver development and both the initiation and termination of liver regeneration. Recent single-cell RNA sequencing studies have corroborated earlier studies that HSC activation involves a diverse array of phenotypic alterations and identified unique HSC populations. This review serves to highlight these many functions of HSCs, and briefly describe recent genetic tools that will help to thoroughly investigate the role of HSCs in hepatic physiology and pathology. Hepatic stellate cells (HSCs) are best known for their production of fibrosis in response to liver injury, but they display many other phenotypes and vital functions. In the normal liver, HSCs help to orchestrate liver development, produce and maintain the basal extracellular matrix (ECM), produce growth factors and cytokines, present antigens, and serve as the body’s main storage depot for retinoids or vitamin A-containing metabolites. Upon liver injury, HSCs lose the retinoid-containing lipid droplets and differentiate into myofibroblasts and proliferate. Single cell sequencing studies have uncovered that activated HSCs display a high degree of cellular heterogeneity for specific functions. Some are more proliferative, while others are more inflammatory, and others more fibrogenic. If liver injury is resolved, HSC numbers will decrease due to a large degree of apoptosis, and remaining HSCs will at least partially dedifferentiate into more quiescent HSCs. These HSCs help remove the fibrotic scar and reestablish the basal ECM scaffold. If liver regeneration is required, HSCs will coordinate this by building of the basal ECM and production of growth factors, cytokines, and angiogenic factors.
