Department of Dermatology and Allergology, University Hospital of the RWTH, Aachen, Germany.
Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
Topical application of pantothenate is widely used in clinical practice for wound healing. Previous studies identified a positive effect of pantothenate on migration and proliferation of cultured fibroblasts. However, these studies were mainly descriptive with no molecular data supporting a possible model of its action. In this study, we first established conditions for an in vitro model of pantothenate wound healing and then analysed the molecular effects of pantothenate. To test the functional effect of pantothenate on dermal fibroblasts, cells were cultured and in vitro proliferation tests were performed using a standardized scratch test procedure. For all three donors analysed, a strong stimulatory effect of pantothenate at a concentration of 20 microg/ml on the proliferation of cultivated dermal fibroblasts was observed. To study the molecular mechanisms resulting in the proliferative effect of pantothenate, gene expression was analysed in dermal fibroblasts cultivated with 20 microg/ml of pantothenate compared with untreated cells using the GeneChip Human Exon 1.0 ST Array. A number of significantly regulated genes were identified including genes coding for interleukin (IL)-6, IL-8, Id1, HMOX-1, HspB7, CYP1B1 and MARCH-II. Regulation of these genes was subsequently verified by quantitative real-time polymerase chain reaction analysis. Induction of HMOX-1 expression by pantothenol and pantothenic acid in dermal cells was confirmed on the protein level using immunoblots. Functional studies revealed the enhanced suppression of free radical formation in skin fibroblasts cultured with panthenol. In conclusion, these studies provided new insight in the molecular mechanisms linked to the stimulatory effect of pantothenate and panthenol on the proliferation of dermal fibroblasts.
泛酸酯的局部应用在临床伤口愈合中得到广泛应用。先前的研究已经确定了泛酸酯对培养的成纤维细胞迁移和增殖的积极影响。然而，这些研究主要是描述性的，没有分子数据支持其作用的可能模型。在这项研究中，我们首先建立了体外泛酸酯伤口愈合模型的条件，然后分析了泛酸酯的分子效应。为了测试泛酸酯对真皮成纤维细胞的功能作用，将细胞培养并通过标准化划痕试验程序进行体外增殖试验。对于分析的所有三个供体，在 20μg/ml 的浓度下观察到泛酸酯对培养的真皮成纤维细胞增殖的强烈刺激作用。为了研究导致泛酸酯增殖作用的分子机制，使用 GeneChip Human Exon 1.0 ST Array 分析了在 20μg/ml 泛酸酯培养的真皮成纤维细胞与未处理细胞之间的基因表达。鉴定出许多显著调节的基因，包括编码白细胞介素（IL）-6、IL-8、Id1、HMOX-1、HspB7、CYP1B1 和 MARCH-II 的基因。随后通过定量实时聚合酶链反应分析验证了这些基因的调节。使用免疫印迹法在蛋白质水平上证实了泛醇和泛酸在真皮细胞中诱导 HMOX-1 表达。功能研究表明，在培养的皮肤成纤维细胞中，泛醇增强了对自由基形成的抑制作用。总之，这些研究为泛酸酯和泛醇对真皮成纤维细胞增殖的刺激作用相关的分子机制提供了新的见解。
