Mechanism of liver fibrosis!

The researchers show that in hepatic stellate cells (HSCs), the main fibrogenic cells in the liver, phosphoenolpyruvate carboxykinase 1 (PCK1)  is reduced in animals and people with fibrosis.

When PCK1 is reduced,  HSC cells undergo metabolic reprogramming characterized by increased glycolysis, become aberrantly activated, and promote liver fibrosis in mice.

PCK1 overexpression reduces acetyl-coenzyme A (CoA), limiting TCA cycle intermediates and ameliorating HSC activation.

Thus, the  study shows that PCK1 protects the liver from scarring by keeping fibrogenic cells in a quiescent state.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(26)00016-1

https://sciencemission.com/Lack-of-PCK1-in-hepatic-stellate-cells