Glucocorticosteroids up-regulate human elastin gene promoter activity in transgenic mice.
Recent characterization of the human elastin gene identified three putative glucocorticoid responsive elements (GRE) within the 5'-flanking DNA. To test the functionality of these cis-elements, transgenic mice that express a human elastin promoter-reporter gene (CAT) construct in a tissue-specific manner were injected with triamcinolone acetonide (TMC) or dexamethasone (DEX), two glucocorticosteroids in clinical use. Subcutaneous injection of these glucocorticoids resulted in a marked, up to 28-fold, enhancement of the CAT activity in the skin at the site of injection. Similarly, intraperitoneal injection of DEX resulted in significant increases in the elastin promoter activity in various internal organs. Furthermore, incubation of skin fibroblast and aortic smooth muscle cell cultures established from the transgenic animals with TMC (10 ng/ml) resulted in marked increases in the elastin promoter activity. These studies demonstrate that glucocorticosteroids act as powerful up-regulators of human elastin promoter activity in transgenic mice.
Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
I
I
Ledo
M
M
Wu
S
S
Katchman
D
D
Brown
S
S
Kennedy
S
S
Hsu-Wong
J
J
Uitto
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004549:Elastin / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012879:Skin Physiological Phenomena; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D003907:Dexamethasone; D004549:Elastin; D014222:Triamcinolone Acetonide