Marín Yarí E, Seiberg Miri, Lin Connie B
The Johnson & Johnson Skin Research Center, CPPW, a unit of Johnson & Johnson Consumer Companies Inc, Skillman, NJ 08558, USA.
Exp Dermatol. 2009 Jul;18(7):611-8. doi: 10.1111/j.1600-0625.2008.00839.x. Epub 2009 Mar 6.
Please cite this paper as: Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival. Experimental Dermatology 2009; 18: 611-618.Abstract: Human skin is endowed with the capacity to synthesize and metabolize steroid hormones, a function of importance in skin physiology and pathology. It is the hormone-regulatory enzymes, including the aldo-keto reductase 1C subfamily (AKR1Cs) that are largely responsible for the local levels of active steroid hormones. AKR1C1 and AKR1C2 inactivate progesterone and 5alpha-dihydrotestosterone, respectively, whereas AKR1C3 activates oestradiol and testosterone. Here, we show that AKR1C1-3 are expressed in keratinocytes and fibroblasts, with marginal expression in melanocytes. In human primary keratinocytes, AKR1C1 and -2 were UVB-inducible in a dose-dependent manner, as shown by quantitative PCR and Western blot analyses. The induction of AKR1C1 by UVB was concomitant with the presence of an apoptotic marker, the cleavage product of poly-ADP ribose polymerase. Similarly, the activation of AKR1C1 and -2 upon UVB exposure was demonstrated in swine skin in vivo and in human skin explants. As expected, hydrogen peroxide-derived reactive oxygen species also induced AKR1C1 and -2 mRNA and protein levels in keratinocytes in a dose-dependent manner. Furthermore, down-regulation of AKR1Cs by small interfering ribonucleic acid led to significantly reduced cell viability. Based on the combined evidence of the presence of an apoptotic marker in the UVB-exposed keratinocytes with increased AKR1Cs expression and reduced cell viability in down-regulated AKR1Cs, we suggest that AKR1C subfamily genes are stress-inducible and might function as survival factors in keratinocytes.
皮肤中的醛酮还原酶1C亚家族基因是紫外线诱导型的：对角质形成细胞存活的可能作用。《实验皮肤病学》2009年；18：611 - 618。摘要：人类皮肤具有合成和代谢甾体激素的能力，这一功能在皮肤生理和病理中具有重要意义。在很大程度上，正是包括醛酮还原酶1C亚家族（AKR1Cs）在内的激素调节酶决定了活性甾体激素的局部水平。AKR1C1和AKR1C2分别使孕酮和5α - 双氢睾酮失活，而AKR1C3激活雌二醇和睾酮。在此，我们表明AKR1C1 - 3在角质形成细胞和成纤维细胞中表达，在黑素细胞中表达较少。在人原代角质形成细胞中，定量PCR和蛋白质印迹分析表明，AKR1C1和 - 2呈剂量依赖性地被紫外线B（UVB）诱导。UVB诱导AKR1C1的同时伴有凋亡标志物多聚ADP核糖聚合酶的裂解产物的出现。同样，在猪的活体皮肤和人皮肤外植体中也证实了UVB照射后AKR1C1和 - 2的激活。正如预期的那样，过氧化氢衍生的活性氧也以剂量依赖性方式诱导角质形成细胞中AKR1C1和 - 2的mRNA及蛋白质水平。此外，小干扰核糖核酸对AKR1Cs的下调导致细胞活力显著降低。基于在暴露于UVB的角质形成细胞中存在凋亡标志物、AKR1Cs表达增加以及下调AKR1Cs后细胞活力降低这些综合证据，我们认为AKR1C亚家族基因是应激诱导型的，可能在角质形成细胞中作为存活因子发挥作用。
