CTGF-mediated ERK signaling pathway influences the inflammatory factors and intestinal flora in ulcerative colitis

• Main Authors: Zhen-Mei Song, Fang Liu, Yan-Ming Chen, Yi-Jing Liu, Xiao-Di Wang, Shi-Yu Du
• Format: Article
• Language: English
• Published: Elsevier 2019-03-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Ulcerative colitis; CTGF; EKR; Inflammatory factors; Intestinal flora
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332218358499

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.