Investigating the Role of ASS1 in Human Hepatic Stellate Cells and its Implication Towards Liver fibrosis

Abstract

Liver Fibrosis is a critical determinant of metabolic dysfunction-associated fatty liver disease (MAFLD) progression and severity. Liver fibrosis initiation and progression is driven by the activation of hepatic stellate cells (HSCs). Metabolic reprogramming has been associated with HSC activation, One of which is Argininosuccinate synthase 1 (ASS1) the key regulator of arginine metabolism. This study aimed to investigate the role of ASS1 in HSC phenotype (proliferation, migration, and invasion) and its implication for liver fibrosis. Using siRNA-mediated ASS1 knockdown and TGF-β induced, found that siASS1 transfection successfully reduces the ASS1 level. This downregulation is sufficient to induce the activation of HSC, which is shown by the increase of fibrogenic markers (α-SMA and COL1A1) comparable to the TGF-β activated HSC model. Our finding revealed that downregulation of ASS1 increased the rate of migration and invasion of HSC compared to the control group. However it is found that the downregulation does not significantly affect the proliferation rate of HSC. These results suggest that ASS1 plays a critical role in modulating HSC activation and phenotypes, where targeting it could provide a novel strategy for mitigating the progression of MAFLD and its complications