Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, U.K.
Newbridge Medical Research Corp., Warren, PA, 16365, U.S.A.
Br J Dermatol. 2015 Nov;173(5):1205-15. doi: 10.1111/bjd.14064. Epub 2015 Oct 11.
Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap-junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model.
To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds.
Wound-edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification.
Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds.
This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers.
已有研究表明,连接蛋白表达的调控改变对于急性伤口修复至关重要。在伤口边缘,缝隙连接蛋白连接蛋白 43 的下调与角质形成细胞和成纤维细胞的迁移有关,而连接蛋白 43 的异常过度表达则显著扰乱了愈合,如链脲佐菌素诱导的糖尿病啮齿动物伤口愈合受损模型所示。
检测多种慢性人伤口中连接蛋白 43 以及连接蛋白 26 和 30 的蛋白表达水平。
从静脉腿部溃疡、糖尿病足或压力性溃疡患者的队列中采集伤口边缘的打孔活检组织和手臂的匹配对照组织。比较每位患者的伤口连接蛋白表达与匹配的非创伤性手臂打孔的表达。使用相同的参数对每位患者的组织进行切片、染色和共聚焦显微镜成像,以进行定量分析。
在所有三种类型的溃疡中,都发现表皮连接蛋白 43、连接蛋白 26 和连接蛋白 30 以及真皮连接蛋白 43 明显上调,这表明连接蛋白上调是慢性伤口之间的共同特征。
这一结果支持靶向连接蛋白 43 以促进慢性溃疡中细胞迁移和伤口愈合的努力。