Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis

• Published in: Digestive diseases and sciences 2022-10, Vol.67 (10), p.4760-4769
• Main Authors: Uchiyama, Kazuhiko, Takagi, Tomohisa, Mizushima, Katsura, Asaeda, Kohei, Kajiwara, Mariko, Kashiwagi, Saori, Minagawa, Yuki, Hotta, Yuma, Tanaka, Makoto, Inoue, Ken, Dohi, Osamu, Okayama, Tetsuya, Yoshida, Naohisa, Katada, Kazuhiro, Kamada, Kazuhiro, Ishikawa, Takeshi, Yasuda, Hiroaki, Konishi, Hideyuki, Kishimoto, Mitsuo, Naito, Yuji, Itoh, Yoshito
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biopsy; Cell growth; Colitis - pathology; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colon - pathology; Cytokines; Dextran; Dextran Sulfate - toxicity; Disease; Gastroenterology; Hepatology; Hospitals; Inflammation; Inflammation - metabolism; Inflammatory bowel disease; Interleukin-8 - genetics; Interleukin-8 - metabolism; Intestinal Mucosa - metabolism; Kinases; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Mice; Monoclonal antibodies; Oncology; Original Article; Pathogenesis; Patients; Peptides; Polymerase chain reaction; Recurrence; Remission (Medicine); RNA; RNA, Messenger - metabolism; Science; Sulfates; Tofacitinib; Transplant Surgery; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Ulcerative colitis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-022-07537-1

Background Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. Aim To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. Methods Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a , TNFα , and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. Results Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. Conclusion Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy.