Abstract
Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF α-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF α-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.
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Acknowledgements
We thank B. Åkerblom and C. Raynoschek for technical assistance, and U. Engström for synthesizing peptides. This study was supported by grants from the Swedish and Finnish Cancer Societies, the Swedish Medical Research Council, the Göran Gustafsson Foundation, the Inga-Britt and Arne Lundberg Foundation, the Swedish Heart and Lung Foundation and the Novo Nordisk Foundation. The cooperative research agreement between the Ludwig Institute for Cancer Research, Stockholm branch, and Fuji Photo Film (Europe) is gratefully acknowledged.
Correspondence and requests for materials should be addressed to U.E. The nucleotide and amino-acid sequences of human PDGF-C have been deposited at GenBank under accession number AF244813.
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Li, X., Pontén, A., Aase, K. et al. PDGF-C is a new protease-activated ligand for the PDGF α-receptor . Nat Cell Biol 2, 302–309 (2000). https://doi.org/10.1038/35010579
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DOI: https://doi.org/10.1038/35010579
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