The PDGF family: four gene products form five dimeric isoforms

Fredriksson, Linda; Li, Hong; Eriksson, Ulf

doi:10.1016/j.cytogfr.2004.03.007

Cited by 676 publications

(547 citation statements)

References 49 publications

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“…7 Ligand dimerization is a requirement for signaling, which occurs when these PDGF dimers bind to and activate 2 structurally related cell surface tyrosine kinase receptors, PDGFRa and PDGFRb. 8 PDGFRa and PDGFRb both are members of the class III receptor tyrosine kinase (RTK) family and have molecular weights of approximately 170 kilo Daltons (kDa) and 180 kDa, respectively. 7 These receptors are the products of 2 homologous genes located on chromosomes 7 and 22, respectively.…”

Section: The Pdgf/pdgfr Axis In Cellular Signalingmentioning

confidence: 99%

Rationale for the development of IMC‐3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet‐derived growth factor receptor α

Shah

Loizos²,

Youssoufian³

et al. 2010

Cancer

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A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor a (PDGFRa) with high affinity and blocks PDGF ligand binding and PDGFRa activation. The results of preclinical studies and the frequent expression of PDGFRa in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies. Cancer 2010;116(4 suppl):1018-26.

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Section: The Pdgf/pdgfr Axis In Cellular Signalingmentioning

confidence: 99%

Rationale for the development of IMC‐3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet‐derived growth factor receptor α

Shah

Loizos²,

Youssoufian³

et al. 2010

Cancer

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show abstract

“…They can form a series of disulfide-linked homo and hetero dimers including PDGF-AA, AB, BB, CC, and DD. 12,13 PDGF works by binding to two distinct cellsurface receptors present on cells of mesenchymal origin. PDGF is released from platelets and macrophages during the earliest phase of fracture healing, 14 and initiates a series of events as a result of its chemotactic and mitogenic properties.…”

mentioning

confidence: 99%

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Al-Zube

Breitbart

O’Connor

et al. 2009

Journal Orthopaedic Research

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Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 mg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. ß

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“…PDGF-A and PDGF-B regulate various physiological and pathophysiological processes, mainly targeting cells of mesenchymal origin (reviewed in Fredriksson et al 1 ).…”

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confidence: 99%

Platelet-derived growth factor isoform expression in carbon tetrachloride-induced chronic liver injury

Borkham-Kamphorst

Коваленко

Roeyen

et al. 2008

Laboratory Investigation

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Platelet-derived growth factor (PDGF) has an essential role in liver fibrogenesis, as PDGF-B and -D both act as potent mitogens on culture-activated hepatic stellate cells (HSCs). Induction of PDGF receptor type-b (PDGFRb) in HSC is well documented in single-dose carbon tetrachloride (CCl 4 )-induced acute liver injury. Of the newly discovered isoforms PDGF-C and -D, only PDGF-D shows significant upregulation in bile duct ligation (BDL) models. We have now investigated the expression of PDGF isoforms and receptors in chronic liver injury in vivo after long-term CCl 4 treatment and demonstrated that isolated hepatocytes have the requisite PDGF signaling pathways, both in the naive state and when isolated from CCl 4 -treated rats. In vivo, PDGF gene expression showed upregulation of all PDGF isoforms and receptors, with values peaking at 4 weeks and decreasing to near basal levels by 8 and 12 weeks. Interestingly, PDGF-C increased significantly when compared to BDL-models. PDGF-A, PDGF-C and PDGF receptor type-a (PDGFRa) correlated closely with inflammation and steatosis. Immunohistochemistry revealed expression of PDGF-B, -C and -D in areas corresponding to centrilobular necrosis, inflammation and fibrosis, whereas PDGF-A localized in regenerative hepatocytes. PDGFRb was identified along the fibrotic septa, whereas PDGFRa showed positive staining in fibrotic septa and regenerative hepatocytes. Despite a significant decline of PDGF isoforms, hepatocyte regeneration peaked at 8 weeks. A marked difference in the degree of fibrosis was observed amongst the individual animals. In summary, PDGF expression in liver damage primarily parallels mesenchymal cell proliferation and extracellular matrix production, rather than hepatocyte regeneration. We conclude that PDGF levels in chronic liver injury peak at 4 weeks after onset of injury, and that the outcome of chronic toxic liver injury strongly depends on the individual capacity for tissue regeneration in the weeks following the peak of PDGF expression.

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The PDGF family: four gene products form five dimeric isoforms

Cited by 676 publications

References 49 publications

Rationale for the development of IMC‐3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet‐derived growth factor receptor α

Rationale for the development of IMC‐3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet‐derived growth factor receptor α

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Platelet-derived growth factor isoform expression in carbon tetrachloride-induced chronic liver injury

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