Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.

ABSTRACT: The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSR^e5-8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSR^e5-8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble control. We treated the scramble control and INSR^e5-8 KO HSCs with insulin or TGFβ and profiled hund

SUBMITTER: Lee WH 

PROVIDER: S-EPMC11871568 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature