Intestinal Epithelial Cell-derived Osteopontin Protects Against Metabolic Dysfunction-associated Steatohepatitis by Modulating Bile Acid Composition and the Gut Microbiome.

ABSTRACT:

Background & aims

The gut-liver axis plays a critical role in metabolic dysfunction-associated steatohepatitis (MASH). Osteopontin (OPN, encoded by SPP1) is implicated in chronic liver disease; however, its expression in intestinal epithelial cells (IECs) and role in MASH remain unclear.

Methods

We evaluated intestinal OPN expression during MASH progression in patients. To determine the function of IEC-derived OPN, we generated Spp1 knock-in (Spp1^{KI IEC}) and knock-out (Spp1^ΔIEC) mice and fed them a high-fat, high-fructose, high-cholesterol diet to induce MASH.

Results

IEC OPN expression decreased with MASH progression and was inversely associated with liver injury. Loss of Spp1 in IECs exacerbated MASH, whereas overexpression or oral OPN administ

SUBMITTER: Han H 

PROVIDER: S-EPMC12804385 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature