Stimulation of Na-dependent phosphate transport by platelet-derived growth factor in rat aortic smooth muscle cells.
We investigated the effect of platelet-derived growth factor B homodimer (PDGF-BB) on inorganic phosphate (Pi) transport activity, which has been reported to be involved in the mechanism of atherosclerosis, in A-10 rat aortic vascular smooth muscle cells (VSMCs). PDGF-BB time- and dose-dependently stimulated Pi transport in A-10 cells. Using northern blot analysis, the PDGF-BB-enhanced Pi transporter (PiT) in A-10 cells was identified as Pit-1 (Glvr-1), a member of the type III Na-dependent PiT. An inhibitor of PDGF beta-receptor tyrosine kinase suppressed PDGF-BB-induced Pi transport. Both a protein kinase C (PKC) inhibitor calphostin C and PKC down regulation suppressed the stimulatory effect of PDGF-BB on Pi transport. On the other hand, inhibition of mitogen-activated protein (MAP) kinases by selective inhibitors did not affect Pi transport. Ly294002, a phosphatidylinositol (PI) 3-kinase inhibitor, partially attenuated PDGF-BB-induced Pi transport. A selective inhibitor of S(6) kinase, rapamycin, reduced this effect of PDGF-BB, while Akt kinase inhibitor did not. In summary, these results indicated that PDGF-BB is a potent and selective stimulator of Pi transport in VSMCs. The mechanism responsible for this effect is not mediated by MAP kinase, but involves activation of PKC, PI 3-kinase and S(6) kinase.
Kakita
Ayako
A
Department of Metabolic Diseases, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Suzuki
Atsushi
A
Nishiwaki
Keiko
K
Ono
Yasunaga
Y
Kotake
Motoko
M
Ariyoshi
Yoh
Y
Miura
Yoshitaka
Y
Ltoh
Mitsuyasu
M
Oiso
Yutaka
Y
D000704:Analysis of Variance; D000818:Animals; D000077214:Becaplermin; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011336:Probability; D011493:Protein Kinase C / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D012964:Sodium; C099852:PDGF receptor tyrosine kinase; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C