Two different PDGF beta-receptor cohorts in human pericytes mediate distinct biological endpoints
2009 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 175, no 1, 171-189 p.Article in journal (Refereed) Published
How activation of a specific growth factor receptor selectively results in either cell proliferation or cytoskeletal reorganization is of central importance to the field of pathophysiology. In this study, we report on a novel mechanism that explains how this process is accomplished. Our current investigation demonstrates that soluble platelet derived growth factor- (PDGF)-BB activates a cohort of PDGF-beta receptors primarily confined to the lipid raft component of the cell membrane, specifically caveolae. In contrast, cell-bound PDGF-BB delivered via cell-cell contact results in activation and the subsequent up-regulation of a cohort of PDGF beta-receptors primarily confined to the non-lipid raft component of the cell membrane. Individual activation of these two receptor cohorts results in distinct biological endpoints, cytoskeletal reorganization or cell proliferation. Mechanistically, our evidence suggests that PDGF-BB-bearing cells preferentially stimulate the non-lipid raft receptor cohort through interleukin 1beta-mediated inhibition of the lipid raft cohort of receptors, leaving the non-raft receptor cohort operational and preferentially stimulated. In human skin injected with PDGF-BB and in tissue reparative processes PDGF beta-receptors colocalize with the caveolae/lipid raft marker caveolin-1. In contrast, in human skin injected with PDGF-BB-bearing tumor cells and in colorectal adenocarcinoma, activated PDGF beta-receptors do not colocalize with caveolin-1. Thus, growth factor receptors are segregated into specific cell membrane compartments that are preferentially activated through different mechanisms of ligand delivery, resulting in distinct biological endpoints.
Place, publisher, year, edition, pages
2009. Vol. 175, no 1, 171-189 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-119729DOI: 10.2353/ajpath.2009.080769ISI: 000267508600016PubMedID: 19497991OAI: oai:DiVA.org:uu-119729DiVA: diva2:300750