Transforming growth factor-beta up-regulates human elastin promoter activity in transgenic mice.
We have recently developed transgenic mice which express approximately 5.2 kb of the human elastin promoter linked to the chloramphenicol acetyl transferase (CAT) reporter gene (J. Biol. Chem. 269:18072-18075, 1994). Previously, transforming growth factor-beta (TGF-beta) has been shown to enhance elastin gene expression, as determined at the mRNA and protein levels. To examine whether this enhancement could be explained by upregulation of the elastin promoter, TGF-beta 1 (100 ng) was injected subcutaneously into the transgenic animals. CAT activity in the skin of treated animals was elevated in a time-dependent manner up to approximately 10-fold after a single injection. These results suggest that the 5.2-kb up-stream segment of the human elastin gene contains cis-elements responsive to TGF-beta 1 in vivo.
Katchman
S D
SD
Department of Dermatology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107.
Hsu-Wong
S
S
Ledo
I
I
Wu
M
M
Uitto
J
J
D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004549:Elastin / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004549:Elastin; D015500:Chloramphenicol O-Acetyltransferase