O'Carroll Simon J, Becker David L, Davidson Joanne O, Gunn Alistair J, Nicholson Louise F B, Green Colin R
Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Methods Mol Biol. 2013;1037:519-46. doi: 10.1007/978-1-62703-505-7_31.
Alterations in Connexin43 (Cx43) expression levels have been shown to play a role in inflammatory processes including skin wounding and neuroinflammation. Cx43 protein levels increase following a skin wound and can inhibit wound healing. Increased Cx43 has been observed following stroke, epilepsy, ischemia, optic nerve damage, and spinal cord injury with gap junctional communication and hemichannel opening leading to increased secondary damage via the inflammatory response. Connexin43 modulation has been identified as a potential target for protection and repair in neuroinflammation and skin wound repair. This review describes the use of a Cx43 specific antisense oligonucleotide (Cx43 AsODN) and peptide mimetics of the connexin extracellular loop domain to modulate Cx43 expression and/or function in inflammatory disorders of the skin and central nervous system. An overview of the role of connexin43 in inflammatory conditions, how antisense and peptide have allowed us to elucidate the role of Cx43 in these diseases, create models of diseases to test interventions and their potential for use clinically or in current clinical trials is presented. Antisense oligonucleotides are applied topically and have been used to improve wound healing following skin injury. They have also been used to develop ex vivo models of neuroinflammatory diseases that will allow testing of intervention strategies. The connexin mimetic peptides have shown potential in a number of neuroinflammatory disorders in ex vivo models as well as in vivo when delivered directly to the injury site or when delivered systemically.
连接蛋白43（Cx43）表达水平的改变已被证明在包括皮肤创伤和神经炎症在内的炎症过程中发挥作用。皮肤受伤后，Cx43蛋白水平会升高，并且会抑制伤口愈合。在中风、癫痫、局部缺血、视神经损伤和脊髓损伤后，已观察到Cx43增加，其间隙连接通讯和半通道开放会通过炎症反应导致继发性损伤增加。连接蛋白43调节已被确定为神经炎症和皮肤伤口修复中保护和修复的潜在靶点。本综述描述了使用Cx43特异性反义寡核苷酸（Cx43 AsODN）和连接蛋白细胞外环结构域的肽模拟物来调节皮肤和中枢神经系统炎症性疾病中Cx43的表达和/或功能。本文概述了连接蛋白43在炎症状态中的作用，反义核酸和肽如何使我们阐明Cx43在这些疾病中的作用，创建疾病模型以测试干预措施以及它们在临床或当前临床试验中的应用潜力。反义寡核苷酸通过局部应用，已被用于改善皮肤损伤后的伤口愈合。它们还被用于开发神经炎症性疾病的体外模型，以测试干预策略。连接蛋白模拟肽在多种神经炎症性疾病的体外模型中以及在直接递送至损伤部位或全身给药时的体内模型中均显示出潜力。
