Intestinal GSTpi deficiency exacerbates the severity of experimental hyperlipidemic acute pancreatitis.

Autor: Yang J; Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, PR China; Wuxi School of Medicine, Wuxi, Jiangsu, PR China. Electronic address: wxdoctory@163.com., Wu B; Wuxi School of Medicine, Wuxi, Jiangsu, PR China., Sha X; Wuxi School of Medicine, Wuxi, Jiangsu, PR China; Xinjiang Production&Construction Corps Hospital, Urumchi, Xinjiang, PR China., Lu H; Wuxi School of Medicine, Wuxi, Jiangsu, PR China., Pan LL; Wuxi School of Medicine, Wuxi, Jiangsu, PR China., Gu Y; Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, PR China. Electronic address: alan89515@163.com., Dong X; Wuxi School of Medicine, Wuxi, Jiangsu, PR China. Electronic address: xldong@jiangnan.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112363. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1016/j.intimp.2024.112363
Abstrakt: Intestinal dysfunction plays a pivotal role in the development of acute pancreatitis (AP), however, the underlying mechanisms of intestinal dysfunction on severity of hyperlipidemic acute pancreatitis (HLAP) are still unclear. Herein, we explored the role of intestinal function on the severity of HLAP. We found that HLAP patients exhibit higher lipid and inflammatory response than AP patients. Hyperlipidemia significantly elevates serum lipids and worsen pancreatic damage in AP mice. In addition, significant exacerbated intestinal barrier damage and inflammation were observed in experimental HLAP mice, as evidenced by increased serum amylase and lipase levels, and pancreatic edema. Further, RNA-Seq showed that a markedly decrease of glutathione S-transferase pi (GSTpi) in colonic tissue of HLAP mice compared with AP mice, accompanied with increased serum lipopolysaccharides level. However, colonic GSTpi overexpression by adeno-associated virus significantly attenuated intestinal damage and subsequent pancreatic inflammation in HLAP mice. Mechanistically, GSTpi mitigated HLAP-mediated colonic NLRP3 inflammasome activation and barrier dysfunction. These results suggest that intestinal GSTpi deficiency exacerbates the severity of experimental HLAP, providing new insights for the clinical treatment of HLAP.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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