Molecular mechanism of the TGFß/Smad7 signaling pathway in ulcerative colitis.
Mol Med Rep
; 25(4)2022 04.
Article
in English
| MEDLINE | ID: covidwho-1753714
ABSTRACT
Aberrant TGFß/Smad7 signaling has been reported to be an important mechanism underlying the pathogenesis of ulcerative colitis. Therefore, the present study aimed to investigate the effects of a number of potential anticolitis agents on intestinal epithelial permeability and the TGFß/Smad7 signaling pathway in an experimental model of colitis. A mouse model of colitis was first established before antiTNFα and 5aminosalicyclic acid (5ASA) were administered intraperitoneally and orally, respectively. Myeloperoxidase (MPO) activity, histological index (HI) of the colon and the disease activity index (DAI) scores were then detected in each mouse. Transmission electron microscopy (TEM), immunohistochemical and functional tests, including Evans blue (EB) and FITCdextran (FD4) staining, were used to evaluate intestinal mucosal permeability. The expression of epithelial phenotype markers Ecadherin, occludin, zona occludens (ZO1), TGFß and Smad7 were measured. In addition, epithelial myosin light chain kinase (MLCK) expression and activity were measured. AntiTNFα and 5ASA treatments was both found to effectively reduce the DAI score and HI, whilst decreasing colonic MPO activity, plasma levels of FD4 and EB permeation of the intestine. Furthermore, antiTNFα and 5ASA treatments decreased MLCK expression and activity, reduced the expression of Smad7 in the small intestine epithelium, but increased the expression of TGFß. In mice with colitis, TEM revealed partial epithelial injury in the ileum, where the number of intercellular tight junctions and the expression levels of Ecadherin, ZO1 and occludin were decreased, all of which were alleviated by antiTNFα and 5ASA treatment. In conclusion, antiTNFα and 5ASA both exerted protective effects on intestinal epithelial permeability in an experimental mouse model of colitis. The underlying mechanism may be mediated at least in part by the increase in TGFß expression and/or the reduction in Smad7 expression, which can inhibit epithelial MLCK activity and in turn reduce mucosal permeability during the pathogenesis of ulcerative colitis.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Colitis, Ulcerative
/
Transforming Growth Factor beta
/
Smad7 Protein
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
Language:
English
Year:
2022
Document Type:
Article
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