Berberine represses Wnt/β-catenin pathway activation via modulating the microRNA-103a-3p/Bromodomain-containing protein 4 axis, thereby refraining pyroptosis and reducing the intestinal mucosal barrier defect induced via colitis

Bioengineered

DeJun Cui¹  Chen Chen¹  Qi Liu²  WenQiang Yuan²  Xun Zhao² 

[1] Department of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang City, Guizhou Province, China;The Graduate School, Guizhou Medical University, Guiyang City, Guizhou Province, China;

关键词: Colitis;    Berberine;    microRNA-103a-3p;    Bromodomain-containing protein 4;    intestinal mucosal barrier defect;   

DOI  :  10.1080/21655979.2022.2047405

来源: DOAJ

【 摘 要 】

Intestinal barrier dysfunction is inflammatory bowel disease’s hallmark. Berberine (BBR) has manifested its anti-inflammatory properties in colitis. For exploring the molecular mechanism of BBR’s impacts on colitis, application of a dextran sodium sulfate-induced mouse colitis in vivo model was with recording the body weight, stool consistency, stool occult blood and general physical symptoms of all groups of mice every day. Behind assessment of intestinal permeability, detection of colon damage’s degree and apoptosis, and inflammatory factors for assessment of pyroptosis was conducted. Application of interleukin-6-stimulated Caco-2 cells was for construction of an in vitro model. Then detection of cell advancement with inflammation and measurement of the barrier’s integrity were put into effect. Verification of microRNA (miR)-103a-3p and Bromodomain-containing protein 4 (BRD4)’s targeting link was conducted. Experiments have clarified BBR, elevated miR-103a-3p or repressive BRD4 was available to alleviate colitis-stimulated pyroptosis and intestinal mucosal barrier defects. BBR elevated miR-103a-3p to target BRD4; Refraining miR-103a-3p or enhancive BRD4 turned around BBR’s therapeutic action on colitis injury. BBR depressed Wnt/β-catenin pathway activation via controlling the miR-103a-3p/BRD4 axis. All in all, BBR represses Wnt/β-catenin pathway activation via modulating the miR-103a-3p/BRD4 axis, thereby mitigating colitis-stimulated pyroptosis and the intestinal mucosal barrier defect. The research suggests BBR is supposed to take on potential in colitis cure.

【 授权许可】

Unknown