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.
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.
Authors: Bruce E Sands; William J Sandborn; Remo Panaccione; Christopher D O'Brien; Hongyan Zhang; Jewel Johanns; Omoniyi J Adedokun; Katherine Li; Laurent Peyrin-Biroulet; Gert Van Assche; Silvio Danese; Stephan Targan; Maria T Abreu; Tadakazu Hisamatsu; Philippe Szapary; Colleen Marano Journal: N Engl J Med Date: 2019-09-26 Impact factor: 91.245
Authors: Brian G Feagan; Paul Rutgeerts; Bruce E Sands; Stephen Hanauer; Jean-Frédéric Colombel; William J Sandborn; Gert Van Assche; Jeffrey Axler; Hyo-Jong Kim; Silvio Danese; Irving Fox; Catherine Milch; Serap Sankoh; Tim Wyant; Jing Xu; Asit Parikh Journal: N Engl J Med Date: 2013-08-22 Impact factor: 91.245
Authors: Brian G Feagan; William J Sandborn; Christopher Gasink; Douglas Jacobstein; Yinghua Lang; Joshua R Friedman; Marion A Blank; Jewel Johanns; Long-Long Gao; Ye Miao; Omoniyi J Adedokun; Bruce E Sands; Stephen B Hanauer; Severine Vermeire; Stephan Targan; Subrata Ghosh; Willem J de Villiers; Jean-Frédéric Colombel; Zsolt Tulassay; Ursula Seidler; Bruce A Salzberg; Pierre Desreumaux; Scott D Lee; Edward V Loftus; Levinus A Dieleman; Seymour Katz; Paul Rutgeerts Journal: N Engl J Med Date: 2016-11-17 Impact factor: 91.245