Department of Medicine , University of Texas Health Science Center , San Antonio 78284 , USA .
J Cell Physiol 164 : 434-40 ( 1995)
Abstract
MBA-2 , bone marrow-derived endothelial stromal cells , express platelet-derived growth factor ( PDGF ) A and B chain mRNAs and secrete PDGF activity that is induced by TGF-beta .
Either chain of the PDGF molecule could modulate hematopoiesis and stromal cell growth .
Intracellular pathways that regulate PDGF expression in the marrow microenvironment are unknown .
In the present study , we examined the mechanisms that mediate PDGF A and B chain mRNA induction by TGF-beta and the role of protein kinase C ( PKC ) and cyclic AMP in PDGF regulation .
TGF-beta was tested in parallel with PMA , an activator of phorbol ester-dependent PKC isoforms .
Both PMA ( 10(-7)M ) and TGF-beta ( 2.5 ng/ml ) increased PDGF A and B chain mRNA levels .
The serine/threonine protein kinase inhibitor , H7 , blocked PDGF A and B chain mRNA induction in response to TGF-beta .
However , down-regulation of PKC by prolonged incubation with PMA failed to abolish TGF-beta induction of PDGF A and B chain mRNAs .
These findings indicate that induction of PDGF A and B chain mRNAs can be mediated via phorbol ester-dependent PKC pathway .
In contrast , H7-sensitive protein kinase(s ) other than phorbol ester-sensitive protein kinase C mediate the effect of TGF-beta .
Agents that increase cAMP were also tested for their effect on PDGF gene expression .
TGF-beta-mediated induction of PDGF A and B chain mRNAs was markedly inhibited by cAMP .
cAMP also blocked stimulation of PDGF A chain mRNA by PMA .
The positive and negative signaling mechanisms involved in modulating PDGF in the microenvironment may be important for determining hematopoietic and stromal cell responses in vivo .