Berberine increases stromal production of Wnt molecules and activates Lgr5+ stem cells to promote epithelial restitution in experimental colitis

BMC Biology

Research Article

Huijuan Liu¹  Zihao Li¹  Wenping Liu²  Haozhong Wang²  Zhengting Wang³  Funeng Geng⁴  Xiuying Ma⁴  Zecheng Luo⁵  Guanlin He⁵  Zheng Liang⁵  Lin Wang⁵  Baojie Li⁶  Lei Shen⁷  Dongdi Wang⁷ 

[1] Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, 610075, Chengdu, China;Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Good Doctor Pharmaceutical Group of Sichuan, 610000, Chengdu, Sichuan, China;Institute of Traditional Chinese Medicine and Stem Cell Research, College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China;Institute of Traditional Chinese Medicine and Stem Cell Research, College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China;Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: Berberine;    Colitis;    ISC;    Wnt;    Circadian rhythm;    Stromal cell;   

DOI  :  10.1186/s12915-022-01492-z

 received in 2022-03-26, accepted in 2022-12-01,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundInflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract,and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%.ResultsHere we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5+ intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules.ConclusionsOur findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-β-Catenin signaling may be a potential target for colitis treatment.

【 授权许可】

CC BY   
© The Author(s) 2022

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