Dataset Information

Lack of intestinal Mucin-1 impairs intestinal epithelial barrier and promotes metabolic dysfunction-associated steatotic liver disease in mice

ABSTRACT: Accumulating evidence suggests that a compromised intestinal epithelial barrier (IEB) contributes to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the exact mechanisms remain unclear. Here we reveal that intestinal mucin 1 (MUC1) levels and glycosylation are decreased in both humans and mice with MASLD. Enterocyte-specific Muc1 knockout aggravates high-fat diet (HFD)-induced IEB impairment and MASLD progression in mice. Mechanistically, HFD feeding reduces the glycosylation of intestinal epithelial MUC1, triggering its clathrin-mediated endocytosis and NEDD4-mediated lysosomal degradation, which subsequently induces β-Catenin degradation and ultimately impaires the IEB. Notably, enterocyte-specific overexpression of cytoplasmic-tail-deleted MUC1 protects against IEB impairment and mitigates MASLD progression. These findings indicate that reduced intestinal epithelial MUC1 levels facilitate the progression of MASLD. Preserving the glycosylation and levels of intestinal MUC1 to maintain IEB integrity is a potential therapeutic strategy to explore for MASLD.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Disease Free

SUBMITTER: Zecheng Li

LAB HEAD: Liang Peng

PROVIDER: PXD066810 | Pride | 2025-12-14

REPOSITORIES: Pride

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Lack of intestinal Mucin-1 impairs intestinal epithelial barrier and promotes metabolic dysfunction-associated steatotic liver disease in male mice.

Li Zecheng Z Gu Runchuan R Liu Donghai D Zhang Yijia Y Qin Yijin Y Li Xinyu X Qiao Yuan Y Li Ziyao Z Guo Jing J Wang Jun J Meng Hua H Peng Liang L

Nature communications 20251205 1

Accumulating evidence suggests that a compromised intestinal epithelial barrier (IEB) contributes to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the exact mechanisms remain unclear. Here we reveal that intestinal mucin 1 (MUC1) levels and glycosylation are decreased in both humans and male mice with MASLD. Enterocyte-specific Muc1 knockout aggravates high-fat diet (HFD)-induced IEB impairment and MASLD progression in male mice. Mechanistically, H ...[more]

PMID: 41350285

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