Mitochondria: A critical hub for hepatic stellate cells activation during chronic liver diseases  

作　　者：Devaraj Ezhilarasan 

机构地区：[1]Department of Pharmacology,the Blue Lab,Molecular Medicine and Toxicology Division,Saveetha Dental College,Saveetha Institute of Medical and Technical Sciences(SIMATS),Chennai 600077,Tamil Nadu,India

出　　处：《Hepatobiliary & Pancreatic Diseases International》2021年第4期315-322,共8页国际肝胆胰疾病杂志（英文版）

摘　　要：Background: Upon liver injury, quiescent hepatic stellate cells(q HSCs), reside in the perisinusoidal space, phenotypically transdifferentiate into myofibroblast-like cells(MFBs). The q HSCs in the normal liver are less fibrogenic, migratory, and also have less proliferative potential. However, activated HSCs(a HSCs) are more fibrogenic and have a high migratory and proliferative MFBs phenotype. HSCs activation is a highly energetic process that needs abundant intracellular energy in the form of adenosine triphosphate(ATP) for the synthesis of extracellular matrix(ECM) in the injured liver to substantiate the injury. Data sources: The articles were collected through Pub Med and EMBASE using search terms "mitochondria and hepatic stellate cells", "mitochondria and HSCs", "mitochondria and hepatic fibrosis", "mitochondria and liver diseases", and "mitochondria and chronic liver disease", and relevant publications published before September 31, 2020 were included in this review. Results: Mitochondria homeostasis is affected during HSCs activation. Mitochondria in a HSCs are highly energetic and are in a high metabolically active state exhibiting increased activity such as glycolysis and respiration. a HSCs have high glycolytic enzymes expression and glycolytic activity induced by Hedgehog(Hh) signaling from injured hepatocytes. Increased glycolysis and aerobic glycolysis(Warburg effect) endproducts in a HSCs consequently activate the ECM-related gene expressions. Increased Hh signaling from injured hepatocytes downregulates peroxisome proliferator-activated receptor-γ expression and decreases lipogenesis in a HSCs. Glutaminolysis and tricarboxylic acid cycle liberate ATPs that fuel HSCs to proliferate and produce ECM during their activation. Conclusions: Available studies suggest that mitochondria functions can increase in parallel with HSCs activation. Therefore, mitochondrial modulators should be tested in an elaborate manner to control or prevent the HSCs activation during liver injury to subsequently regress he

关 键 词：Hepatic stellate cells GLUTAMINOLYSIS GLYCOLYSIS HEDGEHOG MYOFIBROBLASTS 

分 类 号：R575[医药卫生—消化系统]