The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-surgical Adhesion

Alireza Moslem, Rozita Khodashahi, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand
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Abstract

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts are the main mechanism that promotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. As well as, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

以 Connexin43 为靶点的治疗潜力是减少手术后粘连的新方法。
手术后腹膜粘连是一个严重的问题,会导致肠梗阻、不孕和疼痛等并发症。目前还没有预防手术后粘连的有效方法。免疫细胞和粘附的成纤维细胞分泌过多的促炎细胞因子和促纤维化分子是导致术后纤维化疤痕的主要机制。尽管已经对这种疾病的病理原因进行了许多研究,但仍有许多未知的事实,因此,评估不同分子在引起炎症和粘连中的作用可有助于创造新的治疗方法。连接蛋白是一组与间隙连接有关的蛋白质,在相邻细胞间的细胞通讯和信号传递中发挥作用。在不同类型的连接蛋白异构体中,已知连接蛋白43参与了与炎症和纤维化相关的病理状况。最近的研究报告称,通过减少参与粘连形成早期阶段的 α-SMA 和纤溶酶原激活物抑制剂(PAI)等分子的表达,抑制 connexin43 有可能减轻炎症和纤维化。此外,作为预防手术后腹膜粘连的靶点,抑制 connexin43 可能具有治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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