The Effective Hand of Wound Healing: PDGF

  • Platelet derived growth factor (PDGF) is a basic protein stored in platelet alpha particle, and is a low molecular weight cytokinin. It can stimulate a variety of cells, such as fibroblasts which are stagnant in G0/G1 phase, glial cells and smooth muscle cells, to enter the cycle of proliferation. PDGF was discovered in 1974 and named for its origin in platelets. In normal physiological state, PDGF exists in the alpha particles of platelets. When blood coagulates, it is released and activated by disintegrating platelets and has the biological activity of stimulating specific cell chemotaxis and promoting the growth of specific cells. In addition, PDGF can also be synthesized and released by macrophages, vascular smooth muscle cells, fibroblasts, endothelial cells, embryonic stem cells, etc., when tissues are damaged. When liver is damaged, macrophages, platelets, infiltrating inflammatory cells, damaged endothelial cells and activated hepatic astrocytes can all secrete PDGF, which plays a role in an autocrine and paracrine manner. Binding PDGF is a thermostable glycoprotein with a molecular weight of 30KD and is a dimer composed of two polypeptide chains A and B connected by disulfide bond.

    The platelet derived growth factor family includes platelet derived growth factor (PDGF) and vascular endothelial cytokines (VEGF). Each growth factor can be produced by a variety of cells, and its receptor is tyrosine kinase (RTK) type receptor. Platelet derived growth factor family members include: PDGFA, PDGFB, PDGFC, PDGFD, Placental growth factor (PGF), and vascular endothelial growth factor VEGF, VEGF41, VEGFB, VEGFC, FIGF (VEGFD), etc. The common platelet derived factor PDGF is a homotype or heterotype dimer formed by the connection of two polypeptide chains through disulfide bond, which enables PDGF to have various forms of dimer structure, namely PDGF-AA,PDGF-BB,PDGF-AB,PDGF-CC and PDGF-DD.

    Its receptor, PDGFR, is a receptor tyrosine kinase transmembrane glycoprotein dimer molecule, which is distributed in normal endothelial cells, smooth muscle cells, fibroblasts, nerve cells and other cells, and highly expressed in a variety of human tumor cells. PDGFR mainly contains two structurally similar receptor subtypes, PDGFRA and PDGFRB. Ligand molecules of dimers cause the receptor molecules that bind to them to form homologous or heterologous dimers, with three subtypes of ca, aβ and B. Specific binding of PDGF to the receptor leads to the dimerization of the receptor, which leads to the autophosphorylation of the receptor and the activation of the receptor tyrosine kinase. Tyrosine residues expose the binding sites of the SH2 domain /PTB domain to the substrate protein molecules, thus activating the intracellular signal transduction pathway.

    The main functions of PDGF are as follows:1. Promoting pericyte migration and recruitment distribution: PDGFB is an extremely important regulatory gene for vascular maturation and stability during the development process of the body, which can significantly promote the directional migration of pericytes to and around blood vessels; 2. The relationship among PDGF and lymph angiogenesis and lymph node metastasis: PDGFA, B and C have a definite role in promoting lymph angiogenesis, especially PDGFB, which is believed to have s strong role in promoting lymph angiogenesis and has s certain relationship with angiogenesis. Studies have found that PDGFA, B and D may promote tumor growth by promoting tumor lymph angiogenesis, and promote lymph node metastasis of early cervical cancer by promoting tumor lymph angiogenesis; 3. The role of PDGF in other aspects :PDGF is the earliest found connective tissue growth factor, which can promote the growth and differentiation of endothelial cells, glial cells, fibroblasts and vascular smooth muscle cells. After PDCF binds to its receptor, it initiates and amplifies the signal to promote growth through specific tyrosine residues reverse phosphorylation and promote actin rearrangement and chemotaxis.

    It is worth mentioning that, with the application of serum-free neuron culture and other technologies, some new specific protein molecules, such as neurotrophin (NT), have been found in many tissue fluids and extracellular matrix, which, like PDGF, can promote the proliferation, differentiation and survival of neurons. Its receptor is NTRK. The NeuroTrophin Receptor Kinase (NTRK) family consists of three proteins, TRKA, TRKB and TRKC, which are respectively encoded by NTRK1, NTRK2 and NTRK3 genes. These proteins are usually expressed in nerve tissues, and the fusion of NTRK gene would promote the formation of tumors.

    At present, the application of platelet derived growth factor is very extensive in the United States and other developed countries. Recombinant human platelet derived growth factor (rhPDGF) is the only one approved by the FDA as a clinical prescription bioengineering product of the many growth factors. One of its applications is REGRANEX Gel in the form of recombinant human platelet-derived growth factor gel for debridement, healing and repair of advanced diabetic acromegaly ulcer. In addition, great progress has been made in the application of PDGF in the repair of severe burns, skin diseases, bone and tooth defects and regeneration, and joint repair. In conclusion, tumor biology research, drug development and clinical research suggest that PDGF has a series of unknown opportunities and challenges.