PMID- 8392089 OWN - NLM STAT- MEDLINE DCOM- 19930812 LR - 20181113 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 92 IP - 1 DP - 1993 Jul TI - Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts. PG - 425-30 AB - PDGF isoforms have been postulated to serve as mediators of fibroblast proliferation and chemotaxis during lung fibrogenesis induced by asbestos inhalation. We have studied the interaction of chrysotile asbestos fibers with rat lung fibroblasts (RLF) in vitro and the consequent changes in PDGF receptor mRNA expression, PDGF binding, and mitogenic activity of PDGF isoforms. Northern blot analysis revealed that mRNA for the PDGF-receptor alpha subtype (PDGF-R alpha) on RLF was upregulated after a 24-h exposure to asbestos in culture (0.5-15 micrograms fibers/cm2). [125I]PDGF-BB receptor assays showed that normal RLF possess mainly PDGF-R beta and a paucity of PDGF-R alpha. In agreement with the Northern data, saturation binding of [125I]PDGF-BB to RLF exposed to asbestos demonstrated an approximately 40% increase in binding sites accompanied by a twofold decrease in receptor affinity. Treating asbestos-exposed RLF with PDGF-AA, which binds only PDGF-R alpha, blocked the PDGF binding sites that were upregulated by fiber exposure. PDGF-AA had increased mitogenic potency for fiber-exposed RLF, but PDGF-BB was a less potent mitogen for these RLF. Nonfibrogenic carbonyl iron spheres induced similar changes in PDGF growth responses. These data show that inorganic particulates alter the PDGF-R alpha population on RLF without significant change in PDGF-R beta. FAU - Bonner, J C AU - Bonner JC AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. FAU - Goodell, A L AU - Goodell AL FAU - Coin, P G AU - Coin PG FAU - Brody, A R AU - Brody AR LA - eng PT - Journal Article PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Asbestos, Serpentine) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (RNA, Messenger) RN - 1332-21-4 (Asbestos) RN - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor) SB - IM MH - Animals MH - Asbestos/*pharmacology MH - Asbestos, Serpentine MH - Cell Division/drug effects MH - Cells, Cultured MH - Fibroblasts MH - Gene Expression/drug effects MH - In Vitro Techniques MH - Lung/cytology/*metabolism MH - Platelet-Derived Growth Factor/classification/*metabolism MH - RNA, Messenger/genetics MH - Rats MH - Receptors, Platelet-Derived Growth Factor/classification/*genetics/metabolism MH - Up-Regulation PMC - PMC293628 EDAT- 1993/07/01 00:00 MHDA- 1993/07/01 00:01 PMCR- 1993/07/01 CRDT- 1993/07/01 00:00 PHST- 1993/07/01 00:00 [pubmed] PHST- 1993/07/01 00:01 [medline] PHST- 1993/07/01 00:00 [entrez] PHST- 1993/07/01 00:00 [pmc-release] AID - 10.1172/JCI116584 [doi] PST - ppublish SO - J Clin Invest. 1993 Jul;92(1):425-30. doi: 10.1172/JCI116584.