Disease relevance of PDGFC

• Furthermore, we studied how the PDGF-C/tPA axis is regulated in primary fibroblasts and found that PDGF-C expression is down-regulated by hypoxia but induced by transforming growth factor (TGF)-beta1 treatment [1].
• Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma [2].
• Mesangial PDGF-C was markedly upregulated in anti-Thy 1.1 nephritis in parallel with the peak mesangial cell proliferation [3].
• Renal PDGF-C expression was analyzed by immunohistochemistry in normal rats (n = 8), mesangioproliferative anti-Thy 1.1 nephritis (n = 4 each at days 1, 4, 6, and 85), passive Heymann nephritis (PHN, n = 4), puromycin nephrosis (PAN, n = 2), Milan normotensive rats (MN, n = 2), and obese Zucker rats (n = 3) [3].
• PDGF-C protein and the CUB domain of PDGF-C expressed in Escherichia coli, were able to stimulate proliferation of human artery smooth muscle cells, but were inactive on umbilical vein endothelial cells, osteoblasts, fibroblasts, skeletal muscle cells (SkMC), bovine chondrocytes, and rat myocardium cells [4].

High impact information on PDGFC

• PDGF-C protein was not differentially expressed in OA and RA [5].
• PDGF-C and PDGF-D were expressed throughout the SM (lining layer, diffuse infiltrates, and stroma) by both synovial fibroblasts and macrophages [5].
• Platelet-derived growth factor C (PDGF-C) is one of four members in the PDGF family of growth factors, which are known mitogens and survival factors for cells of mesenchymal origin [1].
• PDGF-C is secreted as a latent dimeric factor (PDGF-CC), which undergoes extracellular removal of the CUB domains to become a PDGF receptor alpha agonist [1].
• Inhibition of PDGF-B via specific aptamers reduced the injury in anti-Thy 1.1 nephritis but did not affect the glomerular PDGF-C overexpression or the mitogenicity of PDGF-CC in vitro [3].

Chemical compound and disease context of PDGFC

• We investigated post-translational modification and subcellular localisation of endogenous platelet-derived growth factor-C (PDGF-C) in human thyroid papillary carcinomas (PTC), non-neoplastic thyroid tissues, and a selection of cultured cell lines [6].

Biological context of PDGFC

• 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].
• To determine if PDGF-C signaling contributes to the malignant phenotype of EFT cell lines, we attempted to disrupt this presumed autocrine loop [8].
• The PDGF-C gene was mapped to human chromosome 4q31-32 [4].
• PDGF-C participates in branchial arch morphogenesis and is down-regulated by retinoic acid [9].

Anatomical context of PDGFC

• In addition, we showed that Calu-6 tumors express significant levels of PDGFC, and that the levels of expression of these two PDGFRalpha ligands correlate strongly with the degree of stromal fibroblast infiltration into the tumor mass [10].
• CONCLUSION: PDGF-C and PDGF-D are expressed by synovial fibroblasts and macrophages in RA and OA SMs [5].
• This demonstrates that specific inhibition of PDGF-C signaling in EFT cell lines partially reverts their phenotype [8].
• It is concluded that PDGF-C is a novel mesangial cell mitogen that is constitutively expressed in the kidney and specifically upregulated in mesangial, visceral epithelial, and interstitial cells after predominant injury to these cells [3].
• Dominant negative PDGF-C inhibits growth of Ewing family tumor cell lines [8].

Associations of PDGFC with chemical compounds

• They also suggest that PDGF-C driven signaling may be a possible therapeutic target of more clinically relevant tyrosine kinase inhibitors [8].
• PDGF-C expressed nuclear localisation in 95% of all tested cell types in culture and in 10% of the thyrocytes from both PTC and non-neoplastic tissue [6].

Other interactions of PDGFC

• Furthermore, analysis of a compendium of microarray data revealed significant expression of PDGFA, PDGFC, and PDGFRalpha in human lung tumors [10].
• 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].
• We also show that Arg231 in PDGF-C is essential for tPA-mediated proteolysis and that the released "free" CUB domain of PDGF-C can act as a competitive inhibitor of the cleavage reaction [1].
• There was differential expression of profibrotic and growth factors that while transforming growth factor-beta induced factor, thrombospondin 1, and platelet derived growth factor-C were up-regulated, vascular endothelial growth factor, epidermal growth factor, and fibroblast growth factors 1 and 9 were downregulated [11].
• Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid tissue and cell lines [6].

Analytical, diagnostic and therapeutic context of PDGFC

• Regional and cellular localization of PDGF-C and PDGF-D in the SM was investigated by double-staining immunohistochemistry [5].
• Protein levels of PDGF-C and PDGF-D were quantified by immunoblotting [5].
• Rabbit antisera were generated against human full-length, core domain, and mouse PDGF-C, and their specificity was confirmed by Western blot analyses [3].
• Molecular cloning of SCDGF-B, a novel growth factor homologous to SCDGF/PDGF-C/fallotein [12].

References