OBJECTIVES A healed intestinal mucosa is the aim of therapy in acute ulcerative colitis (UC). Disruption of mucosal wound healing may lead to severe complications including intestinal fibrosis. This study examined mucosal gene expression in the healing process of acute UC with a special focus on known mediators of fibrosis. METHODS Endoscopic biopsies from patients with acute, moderate to severe UC were analyzed with a quantitative polymerase chain reaction array for 84 genes involved in fibrosis pathways. All patients were treated with infliximab (anti- tumor necrosis factor). Biopsies were taken before therapy and when disease remission was reached, defined as a Mayo score of ≤2, with an endoscopic subscore of 0 or 1. A healthy control group was included. Immunostaining of matrix metallopeptidase 9 and smooth muscle actin was performed. RESULTS Mucosal biopsies from acute UC (n = 28), remission UC (n = 28), and healthy controls (n = 13) were analyzed. Fibrosis and extracellular matrix-associated genes were upregulated in the endoscopically healed UC mucosa vs controls, with collagen type III alpha 1 chain, actin alpha 2, lysyl oxidase, TIMP metallopeptidase inhibitor 3, and caveolin 1 uniquely showing no overlap with acute disease. Pro- and antifibrotic mediators (interleukin [IL]13 receptor subunit alpha 2, IL1B, IL10, tumor necrosis factor, snail family transcriptional repressor 1, and C-C motif chemokine ligand 2) were upregulated in both acute and healed UC compared with controls. An attenuated pattern of the canonical transforming growth factor beta (TGFB) pathway was observed in acute UC and to a lesser extent in the healed mucosa, except for TGFB2, which was enhanced. DISCUSSION The endoscopically healed mucosa of UC showed a persisting dysregulation of fibrosis-associated mediators compared with controls, including extracellular matrix remodeling, profibrotic cytokines, and TGFB signaling pathways.

中文翻译：

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急性和愈合的溃疡性结肠炎结肠黏膜中的纤维化介体。

目的治愈肠粘膜是治疗急性溃疡性结肠炎（UC）的目标。破坏粘膜伤口愈合可能导致严重的并发症，包括肠纤维化。这项研究检查了急性UC愈合过程中的黏膜基因表达，并特别关注了纤维化的已知介质。方法采用定量聚合酶链反应阵列分析纤维化途径中涉及的84个基因，对急性，中度至重度UC患者的内镜活检进行分析。所有患者均接受英夫利昔单抗（抗肿瘤坏死因子）治疗。在治疗前和达到疾病缓解时进行活检，定义为Mayo评分≤2，内镜评分为0或1。包括健康对照组。进行基质金属肽酶9和平滑肌肌动蛋白的免疫染色。结果分析了急性UC（n = 28），缓解UC（n = 28）和健康对照组（n = 13）的粘膜活检。纤维化和细胞外基质相关基因在内镜下愈合的UC粘膜与对照组中均被上调，其中胶原III型α1链，肌动蛋白α2，赖氨酰氧化酶，TIMP金属肽酶抑制剂3和小窝蛋白1独特地显示与急性疾病没有重叠。与对照组相比，急性和愈合性UC中的促纤维化和抗纤维化介质（白介素[IL] 13受体亚基α2，IL1B，IL10，肿瘤坏死因子，蜗牛家族转录阻遏物1和CC基序趋化因子配体2）上调。在急性UC中观察到典型转化生长因子β（TGFB）途径的衰减模式，在愈合的粘膜中观察到的程度较小，除了TGFB2增强了。