Isoform-specific regulation of vascular endothelial growth factor (VEGF) family mRNA expression in cultured mouse brown adipocytes.
We have shown that brown adipose tissue (BAT), a thermogenic organ in mammals, expresses high levels of vascular endothelial growth factor (VEGF) mRNA in response to exposure to cold, which may contribute to angiogenesis associated with cold-induced hyperplasia of this tissue. In the present study, we examined mRNA expression of not only VEGF, but also VEGF-B and VEGF-C, recently cloned VEGF isoforms, in vitro using immortal brown adipocytes (HB2) isolated from mouse BAT. HB2 preadipocytes expressed detectable levels of VEGF, VEGF-B and VEGF-C mRNA, but a low level of VEGF. After HB2 cells differentiated into adipocytes, the VEGF mRNA level increased without a noticeable change in the VEGF-B and VEGF-C mRNA levels. When HB2 cells were stimulated by norepinephrine, the VEGF mRNA level increased without a change in that of VEGF-B, while the VEGF-C mRNA level decreased. A marked reduction of VEGF-C mRNA expression was also found when HB2 cells were treated with agonists of peroxisome proliferator-activated receptor gamma (PPARgamma, troglitazone), retinoic acid receptor (RAR, all-trans retinoic acid) and retinoid X receptor (RXR, 9-cis retinoic acid). These results suggest a specific adrenergic mechanism for up-regulation of VEGF expression different from those for other VEGF isoforms, and thereby the major contribution of VEGF to the cold-induced angiogenesis in BAT. In addition, the agonists of PPARgamma, RAR and RXR are suggested to be inhibitory to angiogenesis through the reduction of VEGF-C production.
Asano
A
A
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, 060-0818, Sapporo, Japan. atasano@vetmed.hokudai.ac.jp
Irie
Y
Y
Saito
M
M
D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D018168:Receptors, Retinoic Acid / Q000819:agonists; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000819:agonists; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000322:Adrenergic Agonists; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009638:Norepinephrine