SYK-3BP2 Pathway Activity in Parenchymal and Myeloid Cells Is a Key Pathogenic Factor in Metabolic Steatohepatitis.

ABSTRACT:

Background & aims

Spleen tyrosine kinase (SYK) signaling pathway regulates critical processes in innate immunity, but its role in parenchymal cells remains elusive in chronic liver diseases. We investigate the relative contribution of SYK and its substrate c-Abl Src homology 3 domain-binding protein-2 (3BP2) in both myeloid cells and hepatocytes in the onset of metabolic steatohepatitis.

Methods

Hepatic SYK-3BP2 pathway was evaluated in mouse models of metabolic-associated fatty liver diseases (MAFLD) and in obese patients with biopsy-proven MAFLD (n = 33). Its role in liver complications was evaluated in Sh3bp2 KO and myeloid-specific Syk KO mice challenged with methionine and choline deficient diet and in homozygous Sh3bp2^KI/KI mice with and without SYK expressi

SUBMITTER: Luci C 

PROVIDER: S-EPMC8593618 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature