Regulation of platelet-derived growth factor A and B chain gene expression in bone marrow stromal cells

✍ Scribed by Sherry L. Abboud

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 815 KB
• Volume: 164
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041640224

✦ Synopsis

MBA-2, bone marrow-derived endothelial stromal cells, express platelet-derived growth factor (PDGF) A and B chain mRNAs and secrete PDCF activity that is induced by TGF-beta. Either chain of the PDGF molecule could modulate hematopoiesis and stromal cell growth. lntracellular 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 (10p7M) and TGF-beta (2.5 ngiml) increased PDGF A and B chain mRNA levels. The serineithreonine 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 ki-nas&) 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 PDCF gene expression. TCF-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. o 1995 WiIry-Liss, In[-.