What is it about?
Activation of hepatic stellate cells, a kind of liver nonparenchymal cells, is the key pathogenesis in hepatic fibrosis. Exosomes are extracellular vesicles (EVs) with size of 50–150 nm, secreted from different kinds of cells. It was determined in current work, that exosomes from activated hepatic stellate cells contain glycolysis-related proteins GLUT1 and PKM2. Exosomes released from HSCs were associated with activation and glucose uptake of HSCs. Delivery of exosomes from activated HSCs induced glycolysis of quiescent HSCs, KCs and LSECs. More importantly, it was determined that Hif-1 (hypoxia-inducible factor 1) plays a role in exosome secretion from HSCs and expression of glycolysis-related proteins in HSC exosomes, indicated that Hif-1 acts as a crucial regulator in HSC activation.
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Why is it important?
The current work demonstrated that exosomes secreted by activated HSCs affect metabolic switch of liver nonparenchymal cells via delivery of glycolysis-related proteins and underlined a new mechanism of Hif-1 in metabolic reprogram and activation of HSCs, which is regulating glycolysis via exosomes. These findings represent a novel mechanism, which provides a better understanding about the role of exosomes in HSC activation and pathogenesis of liver fibrosis.
Perspectives
Liver fibrosis is a chronic wound-healing liver injury caused by various factors, including viral hepatitis, alcohol/non-alcoholic steatohepatitis, parasitic infections like schistosomiasis and autoimmune diseases. Our team has been studying the mechanism of hepatic fibrosis from the perspective of activation of hepatic stellate cells. The publication of this article has taken our work to a higher level, which encouraged us. In the future, we will further study the role of glycolysis in the phenotypic and functional changes of various hepatic non-parenchymal cells in liver injury and differential expression of glycolysis-related proteins in serum of patients with different types or stages of liver diseases. I think these studies should be meaningful.
Chunwei Shi
Huazhong University of Science and Technology
Read the Original
This page is a summary of: Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells, The FASEB Journal, July 2019, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201802675r.
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