Platelet-derived growth factor (PDGF) BB homodimer regulates PDGF A- and PDGF B-chain gene transcription in human mesangial cells.
Mesangial cells express platelet-derived growth factor (PDGF) A- and B-chain mRNA and release PDGF. Several polypeptide growth factors, including PDGF itself, induce PDGF A- and B- chain mRNA abundance. To understand the molecular mechanisms associated with the changes in mRNA abundance, we measured the effects of PDGF BB homodimer on PDGF A- and B-chain gene transcription in cultured mesangial cells. The data demonstrate 2- and 4-fold increases in PDGF A-chain gene transcription in response to PDGF BB homodimer at 5 and 24 h time points respectively. PDGF B-chain gene transcription was also induced approximately 3-fold at 2, 5 and 24 h time points in response to treatment with PDGF BB homodimer. The effect of PDGF BB on the half-life of PDGF A- as well as PDGF B-chain mRNA was measured directly by the pulse-chase method. There was no effect on PDGF A-chain mRNA half-life whereas PDGF B-chain mRNA half-life was increased 1.5-fold. These studies indicate that, in human mesangial cells, the increase in the levels of PDGF A- and B-chain mRNA in response to PDGF- receptor(s) activation is mediated at the level of gene transcription. In addition, the regulation of PDGF B- but not PDGF A-chain gene involves increased mRNA stability. Mesangial cells are a useful model for studying molecular mechanisms of PDGF- gene regulation in non-transformed human cells.
Bhandari
B
B
Department of Medicine, University of Texas Health Science Center at San Antonio.
Grandaliano
G
G
Abboud
H E
HE
D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger