The endogenous ligand for guanylate cyclase-C activation reliefs intestinal inflammation in the DSS colitis model

Danfeng  Lan; Yunling  Wen; Xiangqian  Dong; Qin  Yang; Yan  Liu; Kunhua  Wang; Hongying  Li; Yinglei Miao

doi:10.18388/abp.2020_2881

Danfeng Lan 1Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China; 2Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, P.R. China https://orcid.org/0000-0001-7148-1903
Yunling Wen Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, P.R. China
Xiangqian Dong Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, P.R. China
Qin Yang Department of Critical Care Medicine, The First Peoples’ Hospital of Kunming, Kunming, Yunnan, P.R. China
Yan Liu Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, P.R. China
Kunhua Wang Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China https://orcid.org/0000-0002-3374-006X
Hongying Li Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, P.R. China; 3Department of Critical Care Medicine, The First Peoples’ Hospital of Kunming, Kunming, Yunnan, P.R. China; 4Department of General Surgery
Yinglei Miao Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Disease, Kunming, Yunnan, P.R. China

DOI: https://doi.org/10.18388/abp.2020_2881

Abstract

Ulcerative colitis (UC) is a major type of inflammatory bowel disease (IBD) and significantly impacts patient quality of life. Previous research revealed that the guanylate cyclase-C (GC-C) signaling pathway is associated with the severity of UC. We aimed to investigate the effect of the GC-C agonist, guanylin (Gn), on inflammatory injury in mice with colitis. An experimental UC model was established in Balb/c mice. Mesalamine served as a positive control. The Gn overexpression vector was administered once per day for 1 week. Intestinal permeability of the mice was measured using fluorescein isothiocyanate-dextran after the treatment. Histopathologic grading was estimated to assess the inflammatory injury of the colon. The expression level of crucial mediators of the GC-C signaling pathway (Gn, Ugn and GC-C) and tight junction proteins (occludin, claudin-1 and ZO-1) was measured in the colon. Additionally, the level of pro-inflammatory cytokines (IL-8 and TNF-α) in serum was measured. After injecting the UC mice with the Gn overexpression vector, the body weight increased, and the frequency of loose stools and bloody stools was decreased. Intestinal permeability and histopathologic score were significantly reduced (P<0.05). The expression level of GC-C, Gn, Ugn, claudin-1 and ZO-1 was significantly increased (P<0.05). The level of IL-8 and TNF-α in the serum was significantly decreased (P<0.01). Therefore, the application of Gn overexpression vector can ameliorate the intestinal inflammatory injury and repair the mucosal barrier in colitis mice, which further suggests the clinical therapeutic potential of GC-C agonists in IBD.