11β-hydroxysteroid dehydrogenase-1 is a novel regulator of skin homeostasis and a candidate target for promoting tissue repair11β-hydroxysteroid脱氢酶- 1是一种新型调节器的皮肤内稳态和候选目标促进组织修复.pdfVIP

11b-Hydroxysteroid Dehydrogenase-1 Is a Novel Regulator of Skin Homeostasis and a Candidate Target for Promoting Tissue Repair 1 ¤ 1 1 1 1 1 Mika Terao * , Hiroyuki Murota , Akihiro Kimura , Arisa Kato , Akiko Ishikawa , Ken Igawa , Eiji Miyoshi2, Ichiro Katayama1 1 Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan, 2 Department of Molecular Biochemistry and Clinical Investigation, Osaka University, Suita, Osaka, Japan Abstract 11b-hydroxysteroid dehydrogenase 1 (11b-HSD1) catalyzes the interconversion of cortisone and cortisol within the endoplasmic reticulum. 11b-HSD1 is expressed widely, most notably in the liver, adipose tissue, and central nervous system. It has been studied intensely over the last 10 years because its activity is reported to be increased in visceral adipose tissue of obese people. Epidermal keratinocytes and dermal fibroblasts also express 11b-HSD1. However, the function of the enzymatic activity 11b-HSD1 in skin is not known. We found that 11b-HSD1 was expressed in human and murine epidermis, and this expression increased as keratinocytes differentiate. The expression of 11b-HSD1 by normal human epidermal keratinocytes (NHEKs) was increased by starvation or calcium-induced differentiation in vitro. A selective inhibitor of 11b- HSD1 promoted proliferation of NHEKs and normal human dermal fibroblasts, but did not alter the differentiation of NHEKs. Topical application of selective 11 b-HSD1 inhibitor to the dorsal skin of hairless mice caused proliferation of keratinocytes. Taken together, these data suggest that 11 b-HSD1 is involved in tissue remodeling of the skin. This hypothesis was further supported by the