Transcriptional effect of hypoxia on placental leptin.
We observed recentlyl that placental leptin is markedly increased in preeclampsia. Since this disorder is associated with vascular disorders, we have tested the hypothesis that hypoxia regulates leptin expression. We show that hypoxia increased leptin mRNA and secretion in trophoblast-derived BeWo cells. This effect was mediated through leptin promoter activation. 5' deletion analysis allowed us to delineate two regions containing 1.87 kb and 1.20 kb of the promoter which conferred respectively high and low responsiveness to hypoxia. These data indicate that leptin is up-regulated by hypoxia through a transcriptional mechanism likely to involve distinct hypoxia-responsive cis-acting sequences on the promoter.
Grosfeld
A
A
INSERM U 465, Paris, France.
Turban
S
S
André
J
J
Cauzac
M
M
Challier
J C
JC
Hauguel-de Mouzon
S
S
Guerre-Millo
M
M
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D051274:Glucose Transporter Type 3; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000378:metabolism; D015854:Up-Regulation
D017931:DNA Primers; D051274:Glucose Transporter Type 3; D020738:Leptin; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495687:SLC2A3 protein, human; C495690:Slc2a3 protein, rat; D008156:Luciferases