Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFD genes

Background-Platelet-derived growth factor (PDGF), which is a major mitogen for vascular smooth muscle cells and has been implicated in the pathogenesi s of arteriosclerosis, is composed of dimers of PDGF-A and PDGF-B polypepti de chains, encoded by different genes. Here, we have analyzed the chromosom al localization, structure, and expression of 2 newly identified human gene s of the PDGF family, called PDGFC and PDGFD. Methods and Results-We used fluorescence in situ hybridization to locate PD GFC and PDGFD in chromosomes 4q32 and 11q22.3 to 23.2, respectively. Exon s tructures of PDGFC and PDGFD were determined by sequencing from genomic DNA clones. The coding region of PDGFC consists of 6 and PDGFD of 7 exons, of which the last 2 encode the C-terminal PDGF cystine knot growth factor homo logy domain. An N-terminal CUB domain is encoded by exons 2 and 3 of both g enes, and a region of proteolytic cleavage involved in releasing and activa ting the growth factor domain is located in exon 4 in PDGFC and exon 5 in P DGFD. PDGF-C was expressed predominantly in smooth muscle cells and PDGF-D in fibroblastic adventitial cells, and both genes were active in cultured e ndothelial cells and in a variety of tumor cell lines. Both PDGF-C and PDGF -D also stimulated human coronary artery smooth muscle cells. Conclusions-PDGFC and PDGFD have similar genomic structures, which resemble those of the PDGFA and PDGFB genes. Their expression in the arterial wall and cultured vascular cells suggests that they can transduce proliferation/ migration signals to pericytes and smooth muscle cells.