Connexin 43 mimetic peptide Gap27 reveals potential differences in the role of Cx43 in wound repair between diabetic and non-diabetic cells.
Connexin 43 mimetic peptide Gap27 reveals potential differences in the role of Cx43 in wound repair between diabetic and non-diabetic cells.
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DOI：
10.1111/j.1582-4934.2010.01057.x
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发表时间：
2011-04
影响因子：
5.3
通讯作者：
Brandner JM
中科院分区：
文献类型：
--
作者：
Pollok S;Pfeiffer AC;Lobmann R;Wright CS;Moll I;Martin PE;Brandner JM
在早期伤口愈合 (WH) 事件期间，伤口边缘的连接蛋白 43 (Cx43) 下调。在慢性伤口边缘，包括糖尿病伤口，Cx43 表达增强，表明下调对于 WH 很重要。我们之前报道过，Cx43 模拟肽 Gap27 阻断 Cx43 介导的细胞间通讯，并促进体外婴儿细胞的皮肤细胞迁移。在目前的工作中，我们进一步研究了 Gap27 作用的分子机制及其改善皮肤组织以及糖尿病和非糖尿病细胞白质的治疗潜力。使用年轻和老年供体以及糖尿病和非糖尿病来源的离体皮肤、器官模型和人类角质形成细胞/成纤维细胞来评估Gap27对细胞迁移、增殖、Cx43表达、定位、磷酸化和半通道功能的影响。将离体 WH 模型暴露于 Gap27 会减少染料扩散，加速 WH 并提高细胞增殖。在非糖尿病细胞培养物中，Gap27 减少了通过 Cx 半通道的染料摄取，并且在划伤后细胞显示出增强的迁移和增殖。糖尿病来源的细胞在传代早期对 Gap27 不太敏感。在后期传代中，这些细胞表现出与非糖尿病细胞相当的反应。糖尿病细胞和非糖尿病细胞之间差异的原因与糖尿病细胞中 Cx 半通道活性降低相关，但排除了 Cx43 表达、定位和 Ser368 磷酸化的差异。这些数据强调了 Cx43 在 WH 中的重要性，并支持 Gap27 可能是加速正常 WH 的有益疗法的概念。然而，它在糖尿病性白癜风中的使用可能受到限制，我们的结果强调了 Cx43 在不同来源的皮肤细胞中的作用差异。
During early wound healing (WH) events Connexin 43 (Cx43) is down-regulated at wound margins. In chronic wound margins, including diabetic wounds, Cx43 expression is enhanced suggesting that down-regulation is important for WH. We previously reported that the Cx43 mimetic peptide Gap27 blocks Cx43 mediated intercellular communication and promotes skin cell migration of infant cells in vitro. In the present work we further investigated the molecular mechanism of Gap27 action and its therapeutic potential to improve WH in skin tissue and diabetic and non-diabetic cells. Ex vivo skin, organotypic models and human keratinocytes/fibroblasts of young and old donors and of diabetic and non-diabetic origin were used to assess the impact of Gap27 on cell migration, proliferation, Cx43 expression, localization, phosphorylation and hemichannel function. Exposure of ex vivo WH models to Gap27 decreased dye spread, accelerated WH and elevated cell proliferation. In non-diabetic cell cultures Gap27 decreased dye uptake through Cx hemichannels and after scratch wounding cells showed enhanced migration and proliferation. Cells of diabetic origin were less susceptible to Gap27 during early passages. In late passages these cells showed responses comparable to non-diabetic cells. The cause of the discrepancy between diabetic and non-diabetic cells correlated with decreased Cx hemichannel activity in diabetic cells but excluded differences in Cx43 expression, localization and Ser368-phosphorylation. These data emphasize the importance of Cx43 in WH and support the concept that Gap27 could be a beneficial therapeutic to accelerate normal WH. However, its use in diabetic WH may be restricted and our results highlight differences in the role of Cx43 in skin cells of different origin.
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影响因子：
3.9
作者：
Oviedo-Orta, E;Errington, RJ;Evans, WH
通讯作者：
Evans, WH
影响因子：
5.6
作者：
Braet, K;Aspeslagh, S;Leybaert, L
通讯作者：
Leybaert, L
DOI：
10.1016/j.bjps.2004.12.022
发表时间：
2005-07-01
期刊：
BRITISH JOURNAL OF PLASTIC SURGERY
影响因子：
--
作者：
Coutinho, P;Qiu, C;Becker, DL
通讯作者：
Becker, DL
影响因子：
3.7
作者：
Abdullah, KM;Luthra, G;Grazul-Bilska, AT
通讯作者：
Grazul-Bilska, AT
DOI：
10.1073/pnas.012589799
发表时间：
2002-01-08
影响因子：
11.1
作者：
Contreras, JE;Sánchez, HA;Sáez, JC
通讯作者：
Sáez, JC