The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro.

Wright CS; Pollok S; Flint DJBrandner JMMartin PE

摘要

Significant increases in skin wound healing rates occur by reducing connexin-mediated communication (CMC). Gap27, a connexin (Cx) mimetic peptide targeted to the second extracellular loop of Cx43, which inhibits CMC, increases migration of human keratinocytes and dermal fibroblasts. To examine the efficacy of Gap27 in a hyperglycemic and hyperinsulinemic in vitro environment, cell migration, gap junction, and Cx hemichannel functionality and cell-substrate adhesion assays were performed on human dermal fibroblasts and diabetic fibroblast and keratinocytes. To investigate fibroblast genes involved in these processes, extra-cellular matrix (ECM) and adhesion gene expression was determined with a PCR array. Gap27 increased fibroblast migration in both euglycemia/euinsulinemia and hyperglycemia/hyperinsulinemia, and influenced migration in diabetic keratinocytes. Hyperglycemia/hyperinsulinemia reduced gap junction coupling in fibroblasts and Gap27 reduced CMC and cell adhesion to substrata in fibroblasts cultured in high glucose. Migrating dermal fibroblast ECM and cell adhesion genes were found to be differentially regulated by Gap27 in euglycemia and hyperglycemia. The PCR array showed that Gap27 upregulated 34 genes and downregulated 1 gene in euglycemic migrating fibroblasts. By contrast in hyperglycemia, Gap27 upregulated 1 gene and downregulated 9 genes. In euglycemic conditions, Gap27 induced upregulation of genes associated with ECM remodeling, whereas in hyperglycemia, ECM component genes were downregulated by Gap27. Thus, Gap27 improves cell migration during scrape-wound repair in hyperglycemia/hyperinsulinemia conditions in vitro, although migration of diabetic cells is less influenced. Our results suggest that this increase in motility may occur by decreasing gap junction and hemichannel activity and altering gene expression in the adhesion and ECM pathway.

机译：皮肤伤口愈合率明显增加通过减少connexin-mediated通信发生(CMC)。针对第二个细胞外循环Cx43抑制CMC,增加迁移人类角质细胞和真皮成纤维细胞。检查的有效性Gap27高血糖的和血糖在体外环境下,细胞迁移、缝隙连接和残雪hemichannel功能和细胞基质粘附化验进行人类皮肤成纤维细胞和糖尿病患者成纤维细胞和角质细胞。在这些纤维母细胞基因进行调查过程的细胞外基质(ECM)粘附基因表达决心的PCR数组。正常/ euinsulinemia和高血糖和高胰岛素血症和影响在糖尿病性角化细胞迁移。高血糖和高胰岛素血减少差距在成纤维细胞和Gap27结耦合减少CMC和细胞粘附的根基成纤维细胞培养在高葡萄糖。真皮成纤维细胞外基质和细胞粘附基因被发现是由不同吗Gap27在正常和高血糖。34显示Gap27调节基因和数组1表达下调基因euglycemic迁移成纤维细胞。调节1基因和基因表达下调9。euglycemic条件,Gap27诱导upregulation与ECM重塑相关的基因,而在高血糖,ECM组件基因由Gap27表达下调。迁移scrape-wound修复中高血糖和高胰岛素血症条件体外,虽然糖尿病细胞迁移更少的影响。增加可能发生运动性减少差距结和hemichannel活动和改变附着力和ECM通路中的基因表达。

The connexin mimetic peptide Gap27 increases human dermal fibroblast migration in hyperglycemic and hyperinsulinemic conditions in vitro.

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