PDGF Family

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The family of platelet-derived growth factors (PDGFs) belongs to the vascular endothelial growth factor family, with four types of monomers, PDGF-A, PDGF-B, PDGF-C, and PDGF-D, which form homo- or heterodimers through disulfide bonds, including five isoforms, PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, and PDGF-DD. PDGFR is an important member of the PDGF signaling pathway and contains two isoforms, PDGFRα and PDGFRβ. PDGFs are potent pro-mitotic and chemotactic proteins that play a role in the processes of angiogenesis, vascular growth of pre-existing vascular tissues, and mitogenesis, chemotaxis, and directional migration of mesenchymal stromal cells, which are required for early development and wound healing. However, overexpression of PDGF induces diseases such as atherosclerosis, fibrosis, and malignancy.

PDGF production and PDGF receptors specificity in and by pulmonary cells.Figure 1. PDGF production and PDGF receptors specificity in and by pulmonary cells. (Solinc J, et al., 2022)

Studies have demonstrated that cardiomyocyte-specific overexpression of PDGF-A leads to a severe fibrotic response with a multifold increase in heart size, resulting in fatal heart failure in mice within weeks of birth, whereas overexpression of PDGF-B leads only to focal fibrosis and moderate cardiac hypertrophy. In addition, overexpression of myocardial PDGF-D in mice resulted in interstitial fibrosis and dilated cardiomyopathy. All types of PDGF play an important role in myocardial fibrosis and are essential for postinfarction repair.

Renal fibrosis is the underlying pathologic process in chronic kidney disease (CKD) and the best predictor of disease progression. In rodent kidneys with interstitial fibrosis, the expression of all PDGF ligands and receptors is upregulated. PDGF regulates a variety of pathophysiological events, ranging from cell proliferation and migration, extracellular matrix accumulation, as well as the production of proinflammatory and anti-inflammatory mediators, to tissue permeability and hemodynamics. Current studies have found that the use of PDGF-neutralizing antibodies, targeting PDGFRα and PDGFRβ individually, can slow down the progression of renal fibrosis, suggesting that they may be important targets for future anti-renal fibrosis therapies.

Dermal fibroblasts are important effector cells in skin fibrosis, and PDGFs are mitogens of mesenchymal cells involved in skin wound healing. Studies have shown that levels of the inflammatory factor PDGF-B are significantly elevated in the tissues of patients with scarring. In vitro experiments revealed that PDGF-C had strong mitogenic and migratory effects on human skin-derived fibroblasts, and PDGF-C produced by M2-type macrophages also induced the expression of α-smooth muscle actin (α-SMA) in fibroblasts and promoted fibroblast differentiation. Silencing of PDGFRα in fibroblasts from SSC patients using siRNA inhibited fibroblast differentiation to myofibroblasts.

Studies have shown that hepatic fibrosis is due to the activation and proliferation of hepatic stellate cells (HSCs), as well as excessive deposition of extracellular matrix, and PDGFs can effectively promote the activation and proliferation of HSCs. In a study using a rat model, all four isoforms of PDGF were found to be expressed in HSCs that transdifferentiated into myofibroblast-like cells (MFB). Among them, except for PDGF-A, which has little effect, PDGF-B is in the initial stage of transdifferentiation; the expression of PDGF-D increases in the transition period (about 36 days); in the late stage of transdifferentiation, PDGF-C is abundantly expressed, indicating that they play a role in liver fibrosis. play different roles in the process. In addition, overexpression of PDGFs can cause massive proliferation of myofibroblasts as well as stromal collagen accumulation, which in turn triggers pulmonary fibrosis.

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Creative BioMart focuses on the development of GMP proteins and advances scientific research in vascular disease and organ fibrosis by providing a range of high-quality GMP-grade PDGF family cytokines and related customization services. If you are interested in our products or services, please contact us.

Reference

  1. Solinc J, Ribot J, Soubrier F, et al. (2022). The Platelet-Derived Growth Factor Pathway in Pulmonary Arterial Hypertension: Still an Interesting Target?[J]. Life. 12(5): 658.
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