Platelets induce reactive oxygen species-dependent growth of human skin fibroblasts
2003 (English)In: European Journal of Cell Biology, ISSN 0171-9335, E-ISSN 1618-1298, Vol. 82, no 11, 565-571 p.Article in journal (Refereed) Published
A growing amount of evidence suggests that reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, regulate intracellular signalling and have a role in cell proliferation. In the present study, we show that platelets increase the mitogenic rate in human fibroblasts and that this effect was inhibited by the intracellular antioxidant N-acetyl-L-cysteine (NAC) and the NADPH-oxidase inhibitor diphenyleneiodonium chloride (DPI). The mitogenic effects of platelets were mimicked by the platelet factors platelet-derived growth factor BB-isoform (PDGF-BB), transforming growth factor β1 (TGF-β1) and sphingosine-1-phosphate (S1P). The sphingosine kinase inhibitor DL-threo-dihydrosphingosine (DL-dihydro) abrogated the platelet-induced growth, while antibodies directed against PDGF or TGF-β had modest effects. Exposure of fibroblasts to platelets, PDGF-BB, TGF-β1 or S1P caused an extensive intracellular ROS production, measured as changes in dichlorofluorescein fluorescence. This ROS production was totally inhibited by NAC, pyrrolidinethiocarbamate (PDTC), DPI and apocynin. In conclusion, the results presented are indicative of a crucial role of ROS in the platelet-mediated regulation of fibroblast proliferation.
Place, publisher, year, edition, pages
2003. Vol. 82, no 11, 565-571 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-26383DOI: 10.1078/0171-9335-00344ISI: 000187637800004Local ID: 10917OAI: oai:DiVA.org:liu-26383DiVA: diva2:246932