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Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.

Gastroenterology. 2018; 
DuKuo,HyunJeongeun,PremontRichard T,ChoiSteve S,MichelottiGregory A,Swiderska-SynMarzena,DaltonGeorge D,ThelenEric,RiziBahar Salimian,JungYoungmi,DiehlAnna
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Recombinant Proteins Equal amounts of protein were separated by SDS-PAGE gel electrophoresis on 4%-20% Criterion gels (BioRad, Hercules, CA), transferred to PVDF membranes, and incubated with the αSMA (ab32575) or GLS1 (ab156876) primary antibodies OVN at 4°C. Blots were visualized with HRP-conjugated secondary antibodies. β-actin (Genscript, Piscataway, NJ) was used as an internal loading control for immunoblot normalization. Get A Quote

摘要

Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes-associated protein 1 (YAP1 or YAP) and inducing aerobic glycolysis. However, increased aerobic glycolysis alone cannot meet the high metabolic demands of myofibroblastic HSCs. Determining the metabolic processes of these cells could lead to strategies to prevent progressive liver fibrosis, so we investigated whether glutaminolysis (conversion of glutamine to alpha-ketoglutarate) sustains energy metabolism and permits anabolism when Q-HSCs become myofibroblastic, and wheth... More

关键词

Fibrogenesis,Hippo Pathway,Liver Diseases,Metabolic Reprogram