Disease relevance of Pdgfc

• Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects [1].
• In conclusion, our results suggest that PDGF-C signaling is a new mechanism of cleft palate induced by RA [2].
• These studies indicate that hepatic expression of PDGF-C induces a number of profibrotic pathways, suggesting that this growth factor may act as an initiator of fibrosis [3].
• We show that both transient and stable expression of PDGF-C results in the development of liver fibrosis consisting of the deposition of collagen in a pericellular and perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver disease [3].
• Interestingly, PDGF-C expression was ubiquitous in brain tumor cells and tissues but was very low or absent in normal adult and fetal brain [4].

High impact information on Pdgfc

• Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs [1].
• In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion [5].
• PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice [5].
• We further demonstrate that growth of primary fibroblasts in culture is dependent on a tPA-mediated cleavage of latent PDGF-CC, generating a growth stimulatory loop [6].
• Tissue plasminogen activator is a potent activator of PDGF-CC [6].

Chemical compound and disease context of Pdgfc

• Modulation of PDGF-C and PDGF-D expression during bleomycin-induced lung fibrosis [7].

Biological context of Pdgfc

• The mouse Pdgfc gene: dynamic expression in embryonic tissues during organogenesis [8].
• The mouse Pdgfc gene maps to a region of chromosome 17 that is syntenic to human chromosome 6p21.3 In E9 [8].
• Recently, however, the PDGF C and D chains were discovered in a BLAST search of the expressed sequence tag databases [9].
• This study of glioblastoma cells and primary tissues is the first to implicate PDGF-C and -D in brain tumor formation and confirms the existence of autocrine signaling by PDGF-A and -B [4].
• It has not yet been established whether PDGF-C and PDGF-D are linked to disease phenotypes like the classical PDGFs [10].

Anatomical context of Pdgfc

• Contrary to PDGF-A, Pdgfc is not expressed in the central nervous system, except in the cerebellum, and neurogenic derivatives of the neural crest cells [8].
• In the gut and visceral organs, such as the lung and the kidney, Pdgfc mRNA is first expressed in the endodermal epithelium and later in mesenchymal tissues associated with the endodermal structures [8].
• Similar to other PDGFs, Pdgfc is widely expressed in mesenchymal precursors and the myoblast of the smooth and skeletal muscles [8].
• Pdgfc is also absent from the heart and the vascular endothelium[8]
• 5-E15.5 mouse embryo, Pdgfc is widely expressed in the surface ectoderm and later in the germinal layer of the skin, the olfactory and otic placode and their derivatives and the lining of the oral cavity [8].

Associations of Pdgfc with chemical compounds

• PDGF-C Controls proliferation and is down-regulated by retinoic acid in mouse embryonic palatal mesenchymal cells [2].
• Our findings demonstrate that administration of bleomycin to murine lungs leads to a significant increase in PDGF-C mRNA expression and a significant decrease in PDGF-D mRNA expression [7].

Regulatory relationships of Pdgfc

• PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor [5].

Other interactions of Pdgfc

• A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling [1].
• Numerous studies have demonstrated expression of PDGF-A, PDGF-B, and the PDGFRs in gliomablastomas, but such studies have not been conducted for the newly identified PDGF-C and -D [4].
• These observations strongly suggest a role for PDGF-C in bleomycin-induced pulmonary fibrosis [7].

Analytical, diagnostic and therapeutic context of Pdgfc

• Western blot analysis of platelets identified 55-kDa and 80-kDa PDGF C isoforms that were secreted on platelet activation [11].
• Microarray analysis of various cell types showed PDGF C expression in vascular smooth muscle cells, renal mesangial cells, and platelets [11].
• PDGF C mRNA expression in platelets was confirmed by real-time polymerase chain reaction, and PDGF C protein was localized in alpha granules by immuno-gold electron microscopy [11].

References