Deficiency of complement component 3 may be linked to the development of constipation in FVB/N‐C3em1Hlee/Korl mice. Issue 1 (18th December 2020)

• Record Type: Journal Article
• Authors: Park, Ji Won; Kim, Ji Eun; Choi, Yun Ju; Kang, Mi Ju; Choi, Hyeon Jun; Bae, Su Ji; Hong, Jin Tae; Lee, Ho; Hwang, Dae Youn
• Is Part Of: FASEB journal. Volume 35:Issue 1(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-18
• Subjects: complement C3 -- constipation -- knockout mice -- mucin -- stool -- transverse colon; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202000376R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Alterations in complement component 3 (C3) expression has been reported to be linked to several bowel diseases including Crohn's disease, inflammatory bowel disease, and ulcerative colitis; however, the association with constipation has never been investigated. In this study, we aimed to investigate the correlation between C3 regulation and constipation development using a C3 deficiency model. To achieve these, alterations in stool excretion, transverse colon histological structure, and mucin secretion were analyzed in FVB/N‐C3 em1Hlee /Korl (C3 knockout, C3 KO) mice with the deletion of 11 nucleotides in exon 2 of the C3 gene. The stool excretion parameters, gastrointestinal transit, and intestine length were remarkably decreased in C3 KO mice compared with wild‐type (WT) mice, although there was no specific change in feeding behavior. Furthermore, C3 KO mice showed a decrease in mucosal and muscle layer thickness, alterations in crypt structure, irregular distribution of goblet cells, and an increase of mucin droplets in the transverse colon. Mucin secretion was suppressed, and they accumulated in the crypts of C3 KO mice. In addition, the constipation phenotypes detected during C3 deficiency were confirmed in FVB/N mice treated with C3 convertase inhibitor (rosmarinic acid (RA)). Similar phenotypes were observed with respect to stool excretion parameters, gastrointestinal transit, intestine length, alterations in crypt structure, and mucin secretion in RA‐treated FVB/N mice. Therefore, the results of the present study provide the first scientific evidence that C3 deficiency may play an important role in the development of constipation phenotypes in C3 KO mice.