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The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia-inducible factor 1 (Hif-1) regulated HSC activation, and, therefore, we investigated in current work whether Hif-1 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed via electron microscopy, Western blot analysis, and acetylcholinesterase activity. Confocal microscopy was used to measure the uptake of exosomes by quiescent HSCs, Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). Hif-1α was inhibited via 2-ME or specific small interfering RNAs to investigate its role in exosomes derived from HSCs. It was determined that glucose transporter 1 and pyruvate kinase M2 were increasingly expressed in fibrotic liver samples, cell lysates, and exosomes derived from activated HSCs. 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. Disruption of Hif-1 expression suppressed the glycolysis effect delivered by exosomes. Conclusively, our results demonstrated that exosomes secreted by activated HSCs affect the metabolic switch of liver nonparenchymal cells via delivery of glycolysis-related proteins. These findings represent a novel mechanism that contributes to liver fibrosis and has significant implications for new diagnosis and treatment of liver diseases.-Wan, L., Xia, T., Du, Y., Liu, J., Xie, Y., Zhang, Y., Guan, F., Wu, J., Wang, X., Shi, C. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exomes in metabolic switch of liver nonparenchymal cells.
This article was published in the following journal.
Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
The activation of hepatic stellate cells (HSCs) is involved in hepatic fibrogenesis and is regulated by the decreased expression of peroxisome proliferator-activated receptor γ (PPARγ). Rosiglitazon...
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Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.
The process of switching one differentiated cell type into another cell type with a different form and function, such as transdifferentiation from hepatic stellate cells to myofibroblastic cells in liver fibrogenesis.
Solitary or multiple benign hepatic vascular tumors, usually occurring in women of 20-50 years of age. The nodule, poorly encapsulated, consists of a central stellate fibrous scar and normal liver elements such as HEPATOCYTES, small BILE DUCTS, and KUPFFER CELLS among the intervening fibrous septa. The pale colored central scar represents large blood vessels with hyperplastic fibromuscular layer and narrowing lumen.
Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.
Star-shaped, myofibroblast-like cells located in the periacinar, perivascular, and periductal regions of the EXOCRINE PANCREAS. They play a key role in the pathobiology of FIBROSIS; PANCREATITIS; and PANCREATIC CANCER.
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