Differential modulation of fos and jun gene expression by 1,25-dihydroxyvitamin D3.
1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) modulates the mitogenic response to alpha-thrombin either positively or negatively in vascular smooth muscle (VSM) cells depending upon the time at which cells are exposed to 1,25-(OH)2D3. We now examine the impact of 1,25-(OH)2D3 on the induction by alpha-thrombin of c-jun and c-fos mRNA. When 1,25-(OH)2D3 and alpha-thrombin were added simultaneously to rat VSM cells, c-jun expression was enhanced by five-fold compared to cells exposed to thrombin alone. However, when cells were exposed to 1,25-(OH)2D3 for 48h prior to thrombin, c-jun expression after alpha-thrombin was reduced to less than 25% of the level in cells exposed to thrombin alone. c-fos expression after alpha-thrombin was unaffected by 1,25-(OH)2D3. Thus 1,25-(OH)2D3 dramatically alters the ratio of jun/fos mRNA produced during the mitogenic response and may thus modulate the response to mitogens.
Division of Nephrology, University of California, San Francisco 94143.
A H
AH
Tu-Yu
R C
RC
Morris
H E
HE
Ives
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D013917:Thrombin / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D013917:Thrombin; D002117:Calcitriol