Lee Su-Mi, Lee Kyung-Hwa, Park Seon-Young, Kim Dong Hyun, Chung Jin Ook, Ju Jae Kyun, Lee Jae-Hyuk, Kim Hyun Soo
Department of Internal Medicine, Chonnam National University Medical School, 42, Jaebongro, Dong-ku, Gwangju, 501-757, Korea.
Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea.
BMC Gastroenterol. 2021 Mar 20;21(1):129. doi: 10.1186/s12876-021-01713-9.
Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn's disease (CD).
Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients.
The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20-0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03).
Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.
富含半胱氨酸的血管生成诱导因子61（Cyr61）正逐渐成为组织稳态和伤口修复的重要调节因子。我们旨在探讨Cyr61在结肠黏膜中的表达情况，并分析Cyr61表达与克罗恩病（CD）患者临床病程之间的关联。
通过检索病理报告，从83例CD患者和372例对照中获取内镜样本。其中，通过倾向评分法在每组中各选取43例年龄和性别匹配的样本，采用免疫组织化学（IHC）方法比较Cyr61的表达。将CD患者Cyr61表达的IHC评分分为三分位数，以评估其与临床病程的关联。我们还检测了CD患者炎症性和非炎症性结肠黏膜病变中Cyr61及促炎基因的mRNA水平。
CD患者中Cyr61表达的平均IHC评分（86.5）高于对照组（46.1，P < 0.001）。在CD患者中，临床复发患者Cyr61表达的平均IHC评分（68.3）低于未复发患者（92.2，P = 0.01）。炎症黏膜中Cyr61的mRNA水平比非炎症病变中的高两倍（P > 0.05），且CD患者炎症黏膜中IL-6和TLR-4的mRNA水平显著高于非炎症黏膜（均P < 0.05）。根据Cyr61表达的IHC评分将CD患者分为三分位数组时，Cyr61高表达患者的临床复发率往往较低（趋势P = 0.02）。在对CD患者的年龄、性别和结肠镜检查时的CD活动指数进行校正后，与Cyr61表达的第一三分位数相比，第三三分位数与临床复发风险降低相关（OR 0.43，95%CI 0.20 - 0.92，P = 0.03）。
CD患者中Cyr61的黏膜表达与临床病程呈负相关。未来需要考虑开展研究，以评估Cyr61是否可能在激活CD患者的炎症反应以及促进伤口愈合和组织修复中发挥作用。
