PLATELET-DERIVED GROWTH-FACTOR (PDGF) BB HOMODIMER REGULATES PDGF A-CHAIN AND PDGF B-CHAIN GENE-TRANSCRIPTION IN HUMAN MESANGIAL CELLS

被引:8
作者
BHANDARI, B [1 ]
GRANDALIANO, G [1 ]
ABBOUD, HE [1 ]
机构
[1] AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284
关键词
D O I
10.1042/bj2970385
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:385 / 388
页数:4
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