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

被引：5

作者：

Uchiyama, Kazuhiko ^{[1
]}

Takagi, Tomohisa ^{[1
,2
]}

Mizushima, Katsura ^{[1
]}

Asaeda, Kohei ^{[1
]}

Kajiwara, Mariko ^{[1
]}

Kashiwagi, Saori ^{[1
]}

Minagawa, Yuki ^{[1
]}

Hotta, Yuma ^{[1
]}

Tanaka, Makoto ^{[1
]}

Inoue, Ken ^{[1
]}

Dohi, Osamu ^{[1
]}

Okayama, Tetsuya ^{[1
]}

Yoshida, Naohisa ^{[1
]}

Katada, Kazuhiro ^{[1
]}

Kamada, Kazuhiro ^{[1
]}

Ishikawa, Takeshi ^{[1
]}

Yasuda, Hiroaki ^{[1
]}

Konishi, Hideyuki ^{[1
]}

Kishimoto, Mitsuo ^{[3
]}

Naito, Yuji ^{[4
]}

Itoh, Yoshito ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Mol Gastroenterol & Hepatol, Kamigyo Ku, 465 Kajiicho Hirok Kawaramachi, Kyoto 6028566, Japan

[2] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Med Innovat & Translat Med Sci, Kyoto 6028566, Japan

[3] Kyoto City Hosp, Dept Surg Pathol, Kyoto 6048845, Japan

[4] Kyoto Prefectural Univ Med, Dept Human Immunol & Nutr Sci, Kyoto 6028566, Japan

来源：

DIGESTIVE DISEASES AND SCIENCES | 2022年 / 67卷 / 10期

基金：

日本学术振兴会;

关键词：

Wnt-5a; Ulcerative colitis; Relapse; TNF-alpha; IL-8; MAINTENANCE THERAPY; INTERFERON-GAMMA; INDUCTION; CELL; EXPRESSION; DISEASE; USTEKINUMAB; MACROPHAGES; TOFACITINIB; PHENOTYPE;

D O I：

10.1007/s10620-022-07537-1

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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-alpha and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNF alpha, 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-alpha and IL-8 expression. Results Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-alpha 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 alpha 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.

引用

页码：4760 / 4769

页数：10

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