Platelet derived growth factor-A chain gene expression in cultured mesangial cells : regulation by phorbol ester at the level of mRNA abundance , transcription and mRNA stability .

Bhandari B ; Abboud HE

Department of Medicine , University of Texas Health Science Center , San Antonio 78284-7882 .

Mol Cell Endocrinol 91 : 185-91 ( 1993)

Abstract
In human renal mesangial cells , platelet derived growth factor ( PDGF)-A chain is subject to regulation by protein kinase C ( PKC ) activator , phorbol ester ( phorbol 12-myristate 13-acetate , PMA ) . Treatment of mesangial cells with PMA increases PDGF-A chain mRNA abundance as analyzed by Northern blot hybridization . In contrast to the effect of PMA , the inactive analog phorbol had no effect on PDGF-A chain mRNA levels , while the PKC inhibitor H7 markedly reduced the PMA-induced increment in PDGF-A chain mRNA . To determine the mechanism by which PMA increases the abundance of this gene , transcription rate was measured by nuclear transcript elongation assay . Treatment of mesangial cells with PMA resulted in a 2-fold increase in PDGF-A chain gene transcription . In addition , we analyzed the effects of PMA on PDGF-A chain mRNA half-life as measured directly by pulse-chase method . PDGF-A chain mRNA has a half-life of about 106 min. The PDGF-A chain mRNA half-life was reduced by 30% ( t1/2 = 74 min ) when mesangial cells were incubated with PMA . Our results demonstrate that in human renal mesangial cells , the regulation of PDGF-A chain gene expression by PMA is primarily at the level of transcription .