Disease relevance of PDGFD

• Platelet-derived growth factor D induces cardiac fibrosis and proliferation of vascular smooth muscle cells in heart-specific transgenic mice [1].
• Macrophage recruitment was also the characteristic response when PDGF-D was expressed in skeletal muscle or ear by an adeno-associated virus vector [2].
• Here, we examined the expression level of PDGF-D in human renal cell carcinoma by immunohistochemical staining using tissue arrays [3].
• Overexpression of PDGF-D in SN12-C cells promoted tumor growth, angiogenesis, and metastasis of human renal cell carcinoma in an orthotopic severe combined immunodeficient (SCID) mouse model [3].
• A potential oncogenic activity of platelet-derived growth factor d in prostate cancer progression [4].

High impact information on PDGFD

• Platelet-derived growth factor D-chain (PDGF-D) is the newest member of the PDGF family of mitogens and chemoattractants expressed in a wide variety of cell types, including vascular smooth muscle cells (SMCs) [5].
• Inducible platelet-derived growth factor D-chain expression by angiotensin II and hydrogen peroxide involves transcriptional regulation by Ets-1 and Sp1 [5].
• Thus, 2 separate trans-acting factors regulate PDGF-D transcription, alone and in response to oxidative stress [5].
• Platelet-derived growth factor D is activated by urokinase plasminogen activator in prostate carcinoma cells [6].
• When compared with control mice, PDGF-D transgenic mice displayed increased numbers of macrophages and elevated interstitial fluid pressure in the dermis [2].

Chemical compound and disease context of PDGFD

• Inhibition of PDGF-D expression by short hairpin RNA interference (shRNAi) and blockage of PDGFRbeta signaling by Gleevec inhibited the growth and lung metastasis of SN12-C cells grown orthotopically in SCID mice [3].

Biological context of PDGFD

• Exon structures of PDGFC and PDGFD were determined by sequencing from genomic DNA clones [7].
• METHODS AND RESULTS: We used fluorescence in situ hybridization to locate PDGFC and PDGFD in chromosomes 4q32 and 11q22.3 to 23.2, respectively [7].
• We investigated the effects of PDGF-D in transgenic mice by expressing it in basal epidermal cells and then analyzed skin histology, interstitial fluid pressure, and wound healing [2].

Anatomical context of PDGFD

• PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis [2].
• Combined expression of PDGF-D with vascular endothelial growth factor-E (VEGF-E) led to increased pericyte/smooth muscle cell coating of the VEGF-E-induced vessels and inhibition of the vascular leakiness that accompanies VEGF-E-induced angiogenesis [2].

Associations of PDGFD with chemical compounds

• 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 homology domain [7].

Other interactions of PDGFD

• An N-terminal CUB domain is encoded by exons 2 and 3 of both genes, and a region of proteolytic cleavage involved in releasing and activating the growth factor domain is located in exon 4 in PDGFC and exon 5 in PDGFD [7].
• Platelet derived growth factor-D may be a possible therapeutic target for advanced IgA nephropathy [8].

Analytical, diagnostic and therapeutic context of PDGFD

• Molecular cloning of SCDGF-B, a novel growth factor homologous to SCDGF/PDGF-C/fallotein [9].

References