Research progress of JAK-STAT signaling pathway in liver fibrosis
WANG Bingyuan
WU Shihao
LI Jiaxing
WANG Qingwei
LI Mingyi
Abstract：Liver fibrosis is a pathological process caused by aberrant repair following chronic liver injury,with its core mechanisms involving hepatic stellate cell(HSC)activation and excessive extracellular matrix(ECM)deposition.The JAK-STAT signaling pathway plays a dual role in liver fibrosis by regulating inflammatory responses,immune cell polarization,and HSC functions.This review systematically summarizes the regulatory roles of STAT family members(STAT1-6)in liver fibrosis:STAT1 exerts anti-fibrotic effects by promoting NK cell-mediated clearance of activated HSCs and inducing M1 macrophage polarization.STAT2,modulated by the long non-coding RNA Fendrr,may facilitate fibrotic progression.STAT3 exhibits context-dependent actions,driving HSC activation through the IL-6/STAT3/HIF-1α axis while preserving the anti-inflammatory capacity of NK cells.STAT4 and STAT6 promote inflammation-associated fibrosis via the Th1/IFN-γ and Th2/IL-13 pathways,respectively.STAT5 demonstrates protective effects by suppressing TGF-β signaling through growth hormone-dependent mechanisms.Currently,drugs targeting the JAK-STAT pathway(such as the STAT3 inhibitor HJC0123 and traditional Chinese medicine compound QRF)have demonstrated anti-fibrotic potential,highlighting this pathway as a crucial therapeutic target for liver fibrosis.A deeper understanding of the synergistic and antagonistic interactions among STAT proteins will provide novel directions for developing precise anti-fibrotic strategies.
Keywords：liver fibrosisJAK-STAT signaling pathwaySTAT transcription factorshepatic stellate cells(HSCs)targeted therapy
Publication Date：2025-06-30
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 318-324 )