Targeting connexin43 expression accelerates the rate of wound repair
Targeting connexin43 expression accelerates the rate of wound repair
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DOI：
10.1016/j.cub.2003.09.007
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发表时间：
2003-09-30
期刊：
影响因子：
9.2
通讯作者：
Becker, DL
中科院分区：
文献类型：
--
作者：
Qiu, C;Coutinho, P;Becker, DL
组织损伤的修复是所有生物体的关键生存过程，涉及几种细胞类型的协调激活。细胞间通讯显然是这一过程的基础，并且关于伤口部位内通过细胞因子的细胞外通讯已知很多[1，2]。在这里，我们表明，通过连接蛋白43（Cx43）间隙连接通道的直接细胞间通讯[3，4]也在伤口愈合过程中发挥了重要作用。在两个不同的伤口愈合模型，切口和切除皮肤病变，我们表明，一个单一的局部应用的Cx43反义凝胶带来了Cx43蛋白水平的瞬时下调，这导致在伤口闭合率的显着增加。Cx43敲低减少炎症，在宏观上表现为肿胀、发红和伤口裂开的减少，在微观上表现为伤口周围组织中嗜中性粒细胞数量的显著减少。愈合率提高的一个长期结果是肉芽组织沉积程度显著降低，随后形成更小、更少扭曲的瘢痕。这种方法可能在其他受伤组织中具有广泛的治疗应用，并开辟了改善伤口愈合过程的新研究途径。
The repair of tissue damage is a key survival process in all organisms and involves the coordinated activation of several cell types. Cell-cell communication is clearly fundamental to this process, and a great deal is known about extracellular communication within the wound site via cytokines [1, 2]. Here we show that direct cell-cell communication through connexin 43 (Cx43) gap junction channels [3, 4] also plays a major role in the wound healing process. In two different wound healing models, incisional and excisional skin lesions, we show that a single topical application of Cx43 antisense gel brings about a transient downregulation of Cx43 protein levels, and this results in a dramatic increase in the rate of wound closure. Cx43 knockdown reduces inflammation, seen both macroscopically, as a reduction in swelling, redness, and wound gape, and microscopically, as a significant decrease in neutrophil numbers in the tissue around the wound. One long-term consequence of the improved rate of healing is a significant reduction in the extent of granulation tissue deposition and the subsequent formation of a smaller, less distorted, scar. This approach is likely to have widespread therapeutic applications in other injured tissues and opens up new avenues of research into improving the wound healing process.