Downregulation of human type VII collagen (COL7A1) promoter activity by dexamethasone. Identification of a glucocorticoid receptor binding region.
Type VII collagen is the major collagenous component of the anchoring fibrils, attachment structures that stabilize the association of the cutaneous basement membrane zone to the underlying dermis. It is expressed by both epidermal keratinocytes and dermal fibroblasts. In this study, we have examined the pharmacological control of COL7A1 gene expression by the glucocorticorticoid dexamethasone. We demonstrate that dexamethasone is a potent transcriptional inhibitor of COL7A1 promoter activity in dermal fibroblasts, and we identify a potential glucocorticoid response element in the region -318/-212 of the promoter. In addition, we have determined that dexamethasone antagonizes transforming growth factor-beta (TGF-beta) activation of the COL7A1 promoter. This effect occurred without dexamethasone interfering with TGF-beta-induced Smad-specific gene transcription. These results indicate potential deleterious effects of glucocorticosteroids on epidermal wound healing, as reduced COL7A1 expression likely leads to decreased anchoring fibril formation, which may translate into delayed or impaired reepithelialization.
Gras
M P
MP
INSERM U532, H pital Saint-Louis, Paris, France.
Verrecchia
F
F
Uitto
J
J
Mauviel
A
A
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
D005938:Glucocorticoids; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D003094:Collagen