CTGF-mediated ERK signaling pathway influences the inflammatory factors and intestinal flora in ulcerative colitis - 16/02/19
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Graphical abstract |
Highlights |
• | CTGF was up-regulated in the intestinal mucosa tissues of UC patients. |
• | The imbalanced intestinal flora and increased inflammation were showed in UC mice. |
• | Suppression of CTGF improved DSS-induced inflammation and intestinal flora. |
• | Inhibiting CTGF reversed DSS-induced intestinal injury in UC mice via ERK pathway. |
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-1β, 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.
Le texte complet de cet article est disponible en PDF.Keywords : Ulcerative colitis, CTGF, EKR, Inflammatory factors, Intestinal flora
Plan
Vol 111
P. 1429-1437 - mars 2019 Retour au numéro
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