CTGF-mediated ERK signaling pathway influences the inflammatory factors and intestinal flora in ulcerative colitis.
Biomed Pharmacother
; 111: 1429-1437, 2019 Mar.
Article
in En
| MEDLINE
| ID: mdl-30841458
ABSTRACT
OBJECTIVE:
To examine the effect of connective tissue growth factor (CTGF)-mediated ERK signaling pathway on the inflammatory response and intestinal flora in ulcerative colitis (UC).METHODS:
CTGF expression was determined through immunohistochemistry in UC and colon polyp patients. Dextran sulfate sodium (DSS) was used to construct UC models. Wild-type (WT) and CTGF-deficient (CTGF-/-) mice were randomly divided into WT/CTGF-/- + saline, WT/CTGF-/- + DSS, and WT/CTGF-/- + DSS + U0126 (ERK pathway inhibitor) groups. HE staining was conducted to observe the pathological changes in intestinal mucosa. The quantity of intestinal flora was tested in the feces. ELISA, qRT-PCR, and Western blotting were used to detect related-molecules expressions.RESULTS:
CTGF was up-regulated in the intestinal mucosa of UC patients in relation to the severity and grade. Moreover, UC patients showed enhanced the expressions of p-ERK/ERK and pro-inflammatory factors (IL-1ß, IL-6, TNF-α, MPO), increased the quantity of Bacteriodes fragilis (B. fragilis) and Escherichia coli (E. coli), and decreased Bifidobacterium and Lactobacillus. CTGF and pERK/ERK expressions were increased in DSS-induced WT mice, but the pERK expression was lower in CTGF-/- + DSS group than that in the WT + DSS group. U0126 decreased the expressions of pro-inflammatory factors and improved the intestinal flora in WT mice induced with DSS. No significant differences were found in the above indexes between CTGF-/- + DSS group and WT + DSS + U0126 group.CONCLUSION:
Inhibiting CTGF could improve inflammatory response and intestinal flora to partially reverse DSS-induced UC via blocking ERK signaling pathway.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Colitis, Ulcerative
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Inflammation Mediators
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MAP Kinase Signaling System
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Connective Tissue Growth Factor
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Gastrointestinal Microbiome
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
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Animals
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Biomed Pharmacother
Year:
2019
Document type:
Article