Targeting thrombospondin-2 retards liver fibrosis by inhibiting TLR4-FAK/TGF-β signaling.

ABSTRACT:

Background & aims

Thrombospondin-2 (THBS2) expression is associated with liver fibrosis regardless of etiology. However, the role of THBS2 in the pathogenesis of liver fibrosis has yet to be elucidated.

Methods

The in vivo effects of silencing Thbs2 in hepatic stellate cells (HSCs) were examined using an adeno-associated virus vector (serotype 6, AAV6) containing short-hairpin RNAs targeting Thbs2, under the regulatory control of cytomegalovirus, U6 or the α-smooth muscle promoter, in mouse models of carbon tetrachloride or methionine-choline deficient (MCD) diet-induced liver fibrosis. Crosstalk between THBS2 and toll-like receptor 4 (TLR4), as well as the cascaded signaling, was systematically investigated using mouse models, primary HSCs, and human HS

SUBMITTER: Zhang N 

PROVIDER: S-EPMC10877131 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature