PDGF-C Antibody – Rat Monoclonal

Function: Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen and chemoattractant for cells of mesenchymal origin. Required for normal skeleton formation during embryonic development, especially for normal development of the craniofacial skeleton and for normal development of the palate. Required for normal skin morphogenesis during embryonic development. Plays an important role in wound healing, where it appears to be involved in three stages: inflammation, proliferation and remodeling. Plays an important role in angiogenesis and blood vessel development. Involved in fibrotic processes, in which transformation of interstitial fibroblasts into myofibroblasts plus collagen deposition occurs. The CUB domain has mitogenic activity in coronary artery smooth muscle cells, suggesting a role beyond the maintenance of the latency of the PDGF domain. In the nucleus, PDGFC seems to have additional function. Ref.6 Ref.7 Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.22

Subunit structure: Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB domain) with PLAT (via kringle domain)

By similarity. Ref.6 Ref.7

Subcellular location: Cytoplasm. Secreted. Nucleus. Cytoplasmic granule

By similarity. Note: Sumoylated form is predominant in the nucleus. Stored in alpha granules in platelets

By similarity. Membrane associated when bound to receptors

By similarity. Secretion increased by TGFB1. Ref.14 Ref.20

Tissue specificity: Mainly expressed in kidney, testis, liver, heart and brain (at protein level). Highly expressed in airway epithelium, interstitial cells and alveolar macrophages in the lung of mice overexpressing IL13. Expressed in the ovaries. Ref.7 Ref.9 Ref.19 Ref.21 Ref.22

Developmental stage: In stage E9.5-E15.5, 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. In stages E14.5-17.5 expressed in ducts connected to epidermis, and in developing epidermal openings. Highly expressed in the early stages of the developing kidney, in the metanephric mesenchymal aggregates, prefusion skeletal muscle, cardiac myoblasts, and in visceral and vascular smooth muscle. Ref.1 Ref.6 Ref.12 Ref.14

Induction: Expression decreased by hypoxia. Up-regulated by EWS-FLI1 transcription factor in tumor-derived cells. Up-regulated by IL13 overexpression in the lung via STAT6 and EGR1. Elevated expression induced by coxsackievirus B3 infection in immunodeficient mice. Overexpressed in the renal fibrosis. Expression in the lung is significantly increased after bleomycin treatment. Down-regulated by retinoic acid and gonadotropin. Ref.8 Ref.11 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21

Post-translational modification: Proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor-binding epitopes of the core domain. Cleavage after basic residues in the hinge region (region connecting the CUB and growth factor domains) gives rise to the receptor-binding form. Cleaved by PLAT and PLG

By similarity.Sumoylated by SUMO1. Ref.20N-glycosylated

By similarity.

Involvement in disease: Involved in the development of myocarditis and subsequent fibrosis in the experimental model of coxsackievirus B3-induced chronic myocarditis. Ref.16

Disruption phenotype: Perinatal lethality. Mice have feeding and respiratory difficulties due to a complete cleft of the secondary palate. However, they have reduction of renal fibrogenesis. Mice lacking both PDGFA and PDGFC develop a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Ref.15 Ref.22

Sequence similarities: Belongs to the PDGF/VEGF growth factor family.Contains 1 CUB domain.