转录超保守区uc.290高表达促进溃疡性结肠炎肠壁纤维化

Overexpression of transcribed ultraconserved region uc.290 promotes intestinal fibrosis in ulcerative colitis

目的研究转录超保守区uc.290与溃疡性结肠炎(ulcerative colitis,UC)肠壁纤维化之间的关系及作用机制。方法收集2021年1月至2021年10月收治的50例慢性复发型UC住院患者(UC组),选取50例同期收治的结肠息肉内镜下治疗的住院患者(对照组)。两组患者行结肠镜检查并用活检钳获取UC患者结肠炎症部位黏膜及对照组结肠正常黏膜。RT-PCT检测结肠黏膜标本中uc.290、EMT标志性蛋白Vimentin、N-cadherin和E-cadherin的表达,免疫组化检测后三者的表达。采用改良Masson三色染色法检测结肠黏膜中胶原纤维含量并计算纤维化评分。Pearson相关分析uc.290表达与纤维化评分的关系。在模式细胞Caco2中过表达uc.290,RT-PCT、Western blotting分别检测Vimentin、N-cadherin和E-cadherin的表达。结果UC患者结肠黏膜中uc.290显著高表达,纤维化评分显著升高,且uc.290表达水平与纤维化评分呈正相关(r=0.735,P=0.012)。UC患者结肠黏膜及高表达uc.290的Caco2细胞中,Vimentin和N-cadherin显著高表达,而E-cadherin显著低表达。结论uc.290在UC患者结肠黏膜中高表达,通过激活EMT促进肠壁纤维化。

Objective To investigate the change of transcribed ultraconserved region uc.290 expression and its relationship with intestinal fibrosis in ulcerative colitis(UC).Methods 50 hospitalized patients with chronic recurrent UC from Jan.2021 to Oct.2021 were enrolled(UC group).50 hospitalized patients with colon polyps in the same period were enrolled(control group).Colon specimens were taken from inflamed mucosa in UC and normal mucosa in controls during colonoscopy.In colonic specimens,uc.290 expression was detected by RT-PCT.Expressions of Vimentin,N-c adherin and E-cadherin,the marker proteins of EMT,were detected by RT-PCR and immunohistochemistry,respectively.Masson trichrome staining was performed to detect collagen fibers and the fibrosis score was evaluated.Pearson correlation analysis was performed to study the relationship between uc.290 expression level and fibrosis score.In uc.290 overexpressed Caco2 cells,expressions of Vimentin,N-cadherin and E-cadherin were detected by RT-PCT and Western blotting,respectively.Results The expression of uc.290 in the colon mucosa of UC patients was significant high,and the fibrosis score was significantly increased.The expression level of uc.290 was positively correlated with the fibrosis score(r=0.735,P=0.012).Vimentin and N-cadherin were significantly overexpressed in colonic mucosa of UC patients and uc.290 overexpressed Caco2 cells,while E-cadherin was significantly suppressed.Conclusion uc.290 is highly expressed in colonic mucosa of UC patients and promotes intestinal fibrosis by activating EMT.