Osteopontin Regulation of MerTK Macrophages Promotes Crohn's Disease Intestinal Fibrosis

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jul 18

PMID 39021800

Authors

Juanhan Liu

Wenbin Gong

Peizhao Liu

Yangguang Li

Haiyang Jiang

Cunxia Wu

Xiuwen Wu

Yun Zhao

Jianan Ren

Affiliations

Soon will be listed here.

Abstract

The pathogenesis of intestinal fibrosis in Crohn's disease (CD) remains unclear. Mer receptor tyrosine kinase (MerTK) is an immunosuppressive protein specifically expressed in macrophages. Osteopontin (OPN), also known as secreted phosphoprotein 1, contributes to inflammation and wound repair. This study investigates the potential profibrotic pathway in MerTK macrophages in order to provide a possible therapeutic target for intestinal fibrosis. MerTK expression in the inflamed and stenotic bowels was evaluated. The MerTK/ERK/TGF-β1 pathway was overactivated in the fibrotic intestinal tissues of patients with CD. This pathway was induced by epithelial cell apoptosis, resulting in activated fibroblasts with increased TGF-β1 secretion. OPN upregulated TGF production by altering ERK1/2 phosphorylation, as evidenced by OPN or MerTK knockdown and OPN overexpression . MerTK inhibitor UNC2025 alleviated intestinal fibrosis in mouse colitis models, suggesting a potential therapeutic target for intestinal fibrosis in patients with CD.

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