title: Glucocorticoid receptor enhances involucrin expression of keratinocyte in a ligand-independent manner.
abstract: In this study, we investigated the role of glucocorticoid receptor (GR) in epidermal keratinocytes. In adult normal human skin, GR was highly expressed in the upper layers of the epidermis. Consistent with normal skin, GR expression was increased after calcium treatment of HaCaT keratinocytes cultured in vitro, suggesting that GR is involved in keratinocyte differentiation process. Overexpression of GR using an adenovirus showed that expression of involucrin, an early differentiation marker of keratinocytes, was markedly increased due to GR overexpression. However, treatment with dexamethasone, a GR agonist, did not increase involucrin expression. Overexpression of GR led to phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK) in the absence of glucocorticoid, suggesting that the GR effect on involucrin expression is related to activation of intracellular signaling cascades. This idea was supported by the fact that GR-mediated involucrin induction was abolished after treatment with JNK and ERK inhibitors. In addition, GR mutants lacking the ligand-binding domain increased involucrin expression concomitantly with increase of ERK phosphorylation. Together, these results suggest that GR modulates involucrin expression of keratinocytes by regulating the intracellular signaling network in a ligand-independent manner.
authors: Department of Dermatology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon, 301-747, Korea.
authors: Hyun Kyung
authors: HK
authors: Yoon
authors: Zheng Jun
authors: ZJ
authors: Li
authors: Dae-Kyoung
authors: DK
authors: Choi
authors: Kyung-Cheol
authors: KC
authors: Sohn
authors: Eun-Hwa
authors: EH
authors: Lim
authors: Young Ho
authors: YH
authors: Lee
authors: Sooil
authors: S
authors: Kim
authors: Myung
authors: M
authors: Im
authors: Young
authors: Y
authors: Lee
authors: Young-Joon
authors: YJ
authors: Seo
authors: Jeung-Hoon
authors: JH
authors: Lee
authors: Chang Deok
authors: CD
authors: Kim
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism; D010766:Phosphorylation; D011498:Protein Precursors / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D011498:Protein Precursors; D011965:Receptors, Glucocorticoid; C032253:involucrin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases