Deficiency of complement component 3 may be linked to the development of constipation in FVB/N-C3em1Hlee /Korl mice

© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology..

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-C3em1Hlee /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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:35

Enthalten in:

FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 35(2021), 1 vom: 25. Jan., Seite e21221

Sprache:

Englisch

Beteiligte Personen:

Park, Ji Won [VerfasserIn]
Kim, Ji Eun [VerfasserIn]
Choi, Yun Ju [VerfasserIn]
Kang, Mi Ju [VerfasserIn]
Choi, Hyeon Jun [VerfasserIn]
Bae, Su Ji [VerfasserIn]
Hong, Jin Tae [VerfasserIn]
Lee, Ho [VerfasserIn]
Hwang, Dae Youn [VerfasserIn]

Links:

Volltext

Themen:

Cinnamates
Complement C3
Complement C3-C5 Convertases
Constipation
Depsides
EC 3.4.21.-
Journal Article
Knockout mice
Mucin
Research Support, Non-U.S. Gov't
Stool
Transverse colon

Anmerkungen:

Date Completed 15.06.2021

Date Revised 13.12.2023

published: Print

Citation Status MEDLINE

doi:

10.1096/fj.202000376R

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM319024962