Pectic polysaccharides derived from Hainan Rauwolfia ameliorate NLR family pyrin domain-containing 3-mediated colonic epithelial cell pyroptosis in ulcerative colitis

Author:

Yuan Wei1,Tian Yuanyuan2,Lin Cheng2,Wang Yuxuan2,Liu Zhanju3,Zhao Ye4,Chen Fengying2,Miao Xinpu2ORCID

Affiliation:

1. Department of Emergency Surgery, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, China

2. Department of Gastroenterology, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, China

3. Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China

4. Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Abstract

Pectic polysaccharides (PPs) could exert functions on ulcerative colitis (UC), which is classified as a nonspecific inflammatory disorder. This study investigated the molecular mechanism of PPs derived from Rauwolfia in UC. First, the dextran sodium sulfate (DSS)-induced mouse colitis models and lipopolysaccharide (LPS)-treated colonic epithelial cell (YAMC) models were established and treated with PP. Subsequently, the effects of PPs on mucosal damages in DSS mice were detected, and the levels of inflammatory cytokines, pyroptosis-related factors, oxidative stress-related markers, and the tight junction-related proteins in the tissues or cells were examined, and the results suggested that PPs ameliorated colonic mucosal damages and cell pyroptosis in DSS mice, and limited colonic epithelial cell pyroptosis in in vitro UC models. Subsequently, the binding relations of retinol-binding protein 4 (RBP4) to miR-124-3p and NLR pyrin domain-containing 3 (NLRP3) were analyzed. miR-124-3p targeted RBP4 and reduced the binding of RBP4 to NLRP3, thus inhibiting NLRP3-mediated pyroptosis. Finally, functional rescue experiments revealed that miR-124-3p suppression or RBP4 overexpression promoted colonic epithelial cell pyroptosis. Collectively, Rauwolfia-derived PPs limited miR-124-3p and targeted RBP4 and reduced the binding potency of RBP4 to NLRP3 to inhibit NLRP3-mediated pyroptosis, resulting in the alleviation of colonic epithelial cell pyroptosis and mucosal damages in UC.

Funder

Natural Science Foundation of Hainan Province

Education Department of Hainan Province

Publisher

American Physiological Society

Subject

Genetics,Physiology

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