Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Biochem Biophys Res Commun. 2010 Sep 17;400(2):207-11. doi: 10.1016/j.bbrc.2010.08.035. Epub 2010 Aug 13.
Retinoids are regulators of keratinocyte differentiation in the epidermis and important therapeutics in dermatology. The formation of the most active retinoid, all-trans-retinoic acid (RA) by oxidation of retinal is catalyzed by aldehyde dehydrogenases (ALDH), of which ALDH1A3 has been shown to be most efficient. Here we investigated the expression of ALDH1A3 in epidermal cultures. Three alternatively spliced mRNAs of ALDH1A3 were detected in skin cultures with the conventionally spliced mRNA being predominant. Among a panel of ALDH genes, only ALDH1A3 was upregulated by RA in primary keratinocytes. RA increased the expression of ALDH1A3 also in organotypic human skin cultures and in an epidermal explant in vitro whereas no upregulation was detected in dermal fibroblasts and HeLa cells. Our results indicate that the regulation of the retinoic acid metabolism in the epidermis involves transcriptional activation of ALDH1A3, possibly representing a positive feedback loop, which enhances the effect of exogenous RA.
视黄醇是表皮角质细胞分化的调节剂，也是皮肤科的重要治疗药物。视黄醛通过氧化作用形成最活跃的视黄酸（RA），这一过程由醛脱氢酶（ALDH）催化，其中 ALDH1A3 的催化效率最高。本研究旨在调查 ALDH1A3 在表皮培养物中的表达。在皮肤培养物中检测到 ALDH1A3 的三种选择性剪接的 mRNA，其中常规剪接的 mRNA 占主导地位。在一组 ALDH 基因中，只有 ALDH1A3 在原代角质细胞中被 RA 上调。RA 还可增加器官型人皮肤培养物和体外表皮外植体中 ALDH1A3 的表达，但在真皮成纤维细胞和 HeLa 细胞中未检测到上调。我们的结果表明，表皮中视黄酸代谢的调节涉及 ALDH1A3 的转录激活，可能代表一个正反馈回路，增强了外源性 RA 的作用。
