Spitler Ryan, Schwappacher Raphaela, Wu Tao, Kong Xiangduo, Yokomori Kyoko, Pilz Renate B, Boss Gerry R, Berns Michael W
University of California Irvine, Irvine, CA, United States.
Cell Signal. 2013 Dec;25(12):2374-82. doi: 10.1016/j.cellsig.2013.07.029. Epub 2013 Aug 3.
Nitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10μM, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMP-dependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERK were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK).
一氧化氮（NO）供体已被证明可促进伤口愈合，但其机制尚未明确。在此我们表明，新型NO供体亚硝酰钴胺素（NO-Cbi）可改善多种细胞类型的体外伤口愈合，包括一种已建立的肺上皮细胞系和原代人肺成纤维细胞。在摩尔基础上，NO-Cbi比其他两种NO供体更有效，有效的NO-Cbi浓度范围为3至10μM，具体取决于细胞类型。伤口愈合改善继发于细胞迁移增加而非细胞增殖。NO-Cbi的伤口愈合作用由cGMP介导，主要通过I型cGMP依赖性蛋白激酶（PKGI）介导，这是使用药理学抑制剂和激活剂以及靶向I型和II型PKG的小干扰RNA（siRNA）确定的。此外，我们发现Src和ERK是NO-Cbi作用的两个下游介质。我们得出结论，NO-Cbi是细胞迁移和伤口闭合的有效诱导剂，通过cGMP、PKG、Src和细胞外信号调节激酶（ERK）发挥作用。
