关键词: connexin 43 gap junction mucosal immunity ulcerative colitis

来  源:   DOI:10.1515/med-2023-0885   PDF(Pubmed)

Abstract:
The pathogenesis of ulcerative colitis (UC) involves chronic inflammation of the submucosal layer and disruption of epithelial barrier function within the gastrointestinal tract. Connexin 43 (Cx43) has been implicated in the pathogenesis of intestinal inflammation and its associated carcinogenic effects. However, a comprehensive analysis of Cx43\'s role in mucosal and peripheral immunity in patients with UC is lacking. In this study, the colon tissues of patients with UC exhibited severe damage to the intestinal mucosal barrier, resulting in a significant impairment of junctional communication as observed by transmission electron microscopy. The mRNA expression of Cx43 was found to be significantly elevated in the UC group compared to the control group, as determined using the Affymetrix expression profile chip and subsequently validated using qRT-PCR. The immunofluorescence analysis revealed a significantly higher mean fluorescence intensity of Cx43 in the UC group compared to the control group. Additionally, Cx43 was observed in both the cell membrane and nucleus, providing clear evidence of nuclear translocation. The proportion of Cx43 in the UC group for CD4+ and CD8+ T lymphocytes was increased in the control group, but only the proportion of Cx43 for CD8+ T lymphocytes showed significant difference by flow cytometry. The involvement of Cx43 in the pathogenesis of UC and its potential role in mucosal immunity warrants further investigation, as it holds promise as a prospective biomarker and therapeutic target for this condition. The proportion of Cx43 in the UC group for CD4+ and CD8+ T lymphocytes was increased in the control group, but only the proportion of Cx43 for CD8+ T lymphocytes showed a significant difference.
摘要:
溃疡性结肠炎(UC)的发病机制涉及粘膜下层的慢性炎症和胃肠道内上皮屏障功能的破坏。连接蛋白43(Cx43)与肠道炎症的发病机理及其相关的致癌作用有关。然而,缺乏对Cx43在UC患者黏膜和外周免疫中作用的综合分析。在这项研究中,UC患者的结肠组织表现出肠粘膜屏障的严重损伤,导致透射电子显微镜观察到的交界交流显着受损。与对照组相比,UC组Cx43的mRNA表达显著升高,如使用Affymetrix表达谱芯片确定的,随后使用qRT-PCR进行验证。免疫荧光分析显示,与对照组相比,UC组中Cx43的平均荧光强度显著更高。此外,在细胞膜和细胞核中都观察到Cx43,提供核易位的明确证据。UC组CD4+、CD8+T淋巴细胞Cx43比例较对照组升高,但是通过流式细胞术,只有CD8T淋巴细胞的Cx43比例显示出显着差异。Cx43参与UC的发病机制及其在粘膜免疫中的潜在作用有待进一步研究。因为它有望成为这种疾病的前瞻性生物标志物和治疗靶标。UC组CD4+、CD8+T淋巴细胞Cx43比例较对照组升高,但只有Cx43占CD8+T淋巴细胞的比例存在显著差异。
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