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American Journal of Pathology, Vol 126, 7-12, Copyright © 1987 by American Society for Investigative Pathology


REGULAR ARTICLES

Cultured human endothelial cells express platelet-derived growth factor A chain

T Collins, JS Pober, MA Gimbrone Jr, A Hammacher, C Betsholtz, B Westermark and CH Heldin

Four principal cell types involved in the pathophysiologic response of the vessel wall--endothelial cells, smooth muscle cells, platelets, and monocyte/macrophages--secrete platelet-derived growth factor-like (PDGF- like) mitogenic activities. Extensive structural data on these activities exist only for the mitogen produced by platelets, which is a 30-kd dimeric protein composed of structurally related A and B polypeptide chains encoded by different genes. It was previously demonstrated that normal cultured endothelial cells transcribe mRNA encoding the B chain of PDGF from the c-sis gene. Here several new structural features of the mitogen produced by cultured vascular endothelial cells are shown. Hybridization analysis of RNA from normal cultured human umbilical vein endothelial (HUVE) cells revealed that they contain three PDGF A chain transcript species. These RNA species comigrated with and appeared to have the same relative abundance as the three RNA species previously identified in RNA from two human tumor cell lines. A chain transcripts were not identified in RNA from a strain of bovine aortic endothelial cells or in human dermal fibroblasts. The A chain transcripts in HUVE had the same relative abundance as the B chain transcripts. Immunoprecipitation of metabolically labeled endothelial conditioned medium with anti-PDGF antiserum revealed a 31-kd species which was split by reduction and alkylation into two species of 16.5 and 17 kd. Thus, endothelial cells secrete a dimeric mitogen antigenically related to PDGF, with a structure identical to previously isolated PDGF A-chain homodimer. These findings are consistent with the possibility that secretion of PDGF by human endothelial cells may be regulated independently of B- chain expression.


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M Hellstrom, M Kal n, P Lindahl, A Abramsson, and C Betsholtz
Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse
Development, January 6, 1999; 126(14): 3047 - 3055.
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Copyright © 1987 by the American Society for Investigative Pathology.