Fig. 8: A graphical abstract of the role of macrophage TIM3 in NASH fibrosis.

In normal liver, miR-4524a-5p in macrophages suppresses TBP/TIM3/PI3K/AKT/mTOR/TGFβ signaling, and HSCs remain quiescent. In fibrotic NASH, TBP/TIM3 signaling is restored by suppression of miR-4524a-5p. β-TrCP-mediated TIM3 ubiquitination and activation leads to PI3K/AKT/mTOR suppression and TGF-β induction, and the resulting increase and secretion of TGF-β from these macrophages activates HSCs.