Published online Apr 28, 2018. doi: 10.3748/wjg.v24.i16.1766
Peer-review started: February 13, 2018
First decision: March 9, 2018
Revised: March 14, 2018
Accepted: March 31, 2018
Article in press: March 31, 2018
Published online: April 28, 2018
Mucosal healing is a desired therapeutic end-point in the treatment of inflammatory bowel disease (IBD). However, thorough treatment of IBD is difficult and there are some adverse reactions. According to studies, corticotropin-releasing hormone (CRH)-receptor (R)2 can activate the inflammatory response of intestinal mucosa. Our preliminary study found that Tong-Xie-Yao-Fang could lower CRH-R1, increase the expression of CRH-R2, and participates in reconstruction of the intestinal barrier.
Mucosal healing is a desired therapeutic end-point in the treatment of IBD. However, the mechanism of mucosal healing is still unclear.
To explore the significance of CRH-R2 in the mucosal healing of dextran sulfate sodium (DSS)-induced colitis and study the effect of Tong-Xie-Yao-Fang (TXYF) on CRH-R2.
Ulcerative colitis (UC) was induced in mice by administration of 3% (w/v) DSS for 7 d. Then, mice were administered urocortin (Ucn)-2 or various doses of aqueous TXYF extracts, the CRH-R2 antagonist Astressin (Ast)2B, Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. The colitis disease activity index (DAI) was assessed to evaluate the condition of colitis. The expression level of Ki-67 represented the proliferation of colonic epithelial cells. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined by PCR and enzyme-linked immunosorbent assay.
Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths, and higher DAI and histological scores. Additionally, the Ast2B group showed increased intestinal permeability, improved secretion of inflammatory cytokines in colon tissue and reduced colonic epithelial cell proliferation. Increased apoptosis was also demonstrated. The Ucn2 group demonstrated lower DAI and histological scores. Diminished weight loss, longer colon length, reduced intestinal permeability, inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation were all observed. Reduced apoptosis was also observed.
CRH-R2 activates the intestinal mucosal antiinflammatory response and plays an important antiinflammatory role. TXYF promotes the mucosal repair process in colitis mice.
The CRH-R2 signaling pathway plays a pivotal role in mucosal healing in experimental UC in mice. Mucosal healing is a desired therapeutic end-point in the treatment of IBD. Thus, the findings of this study indicate a new potential mechanism by which CRH-R2 treats UC. TXYF, which has fewer side effects than other medicines, promotes the mucosal repair process of colitis mice by regulating CRH-R2. Therefore, TXYF can be used in patients with UC to promote their mucosal repair.