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Updated: Jul 5, 2025

Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
Loss of Mptx2 alters bacteria composition and intestinal homeostasis potentially by impairing autophagy
Weihui Yan1,2,3, Shanshan Chen1,2, Ying Wang1,2,3
1Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
A recent single-cell survey of the small-intestinal epithelium suggests that mucosal pentraxin 2 (Mptx2) is a new Paneth cell marker, but its function and involved mechanism in the Paneth cell are still unknown. Therefore, we create Mptx2 knockout (Mptx2-/-) mice to investigate its precise effects on intestinal homeostasis using models of lipopolysaccharide (LPS), methicillin-resistant Staphylococcus aureus (MRSA) peritoneal infection, and dextran sulfate sodium (DSS)-induced intestinal injury and inflammation. We here find that Mptx2 is selectively expressed in Paneth cells in the small intestines of mice. Mptx2-/- mice have increased susceptibility to intestinal inflammation and injured. Mptx2 deficiency reduces Paneth cell count and expression of antimicrobial factors, leading to altered intestinal bacteria composition. Loss of Mptx2 aggravates MRSA infection-induced damage in the intestine while decreasing autophagy in Paneth cells. Mptx2-/- mice are more vulnerable to LPS-induced intestinal possibly due to inhibition of the autophagy/endoplasmic reticulum (ER) stress pathway. Mptx2-/- mice are susceptible to DSS-induced colitis that could be ameliorated by treatment with gentamicin or vancomycin antibiotics. In conclusion, Mptx2 is essential to maintain intestinal homeostasis potentially via regulation of autophagy in Paneth cells.
Insights
Mucosal pentraxin 2 (Mptx2) is vital for maintaining intestinal homeostasis. Its absence in Paneth cells increases susceptibility to inflammation and infection by disrupting gut bacteria and autophagy.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Mucosal pentraxin 2 (Mptx2) is identified as a novel Paneth cell marker in the small intestine.
- The precise function and regulatory mechanisms of Mptx2 within Paneth cells remain largely unexplored.
Purpose of the Study:
- To elucidate the role of Mptx2 in intestinal homeostasis and Paneth cell function.
- To investigate the impact of Mptx2 deficiency on intestinal responses to infection and injury.
Main Methods:
- Generation and utilization of Mptx2 knockout (Mptx2-/-) mice.
- Modeling intestinal inflammation and injury using lipopolysaccharide (LPS), methicillin-resistant Staphylococcus aureus (MRSA) infection, and dextran sulfate sodium (DSS).
Main Results:
- Mptx2 is selectively expressed in mouse small intestinal Paneth cells.
- Mptx2-/- mice exhibit heightened susceptibility to intestinal inflammation, injury, and MRSA infection.
- Mptx2 deficiency leads to reduced Paneth cell numbers, decreased antimicrobial factor expression, altered gut microbiota, and impaired Paneth cell autophagy.
- Mptx2 deficiency exacerbates LPS-induced intestinal issues, potentially by inhibiting the autophagy/endoplasmic reticulum (ER) stress pathway.
Conclusions:
- Mptx2 plays a critical role in maintaining intestinal homeostasis.
- Mptx2 is essential for Paneth cell function, potentially through the regulation of autophagy.
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