Platelet derived growth factor (PDGF) is a basic protein stored in alpha particles of platelets and is a low molecular weight mitogen.
PDGF can stimulate various cells such as fibroblasts, glial cells, and smooth muscle cells that are stagnated in the G0/G1 phase to enter the division and proliferation cycle. Platelet-derived growth factor PDGF was discovered in 1974 as a peptide regulator that stimulates the growth of connective tissue and other tissue cells. It is named because it is derived from platelets. It exists in the alpha particles of platelets under normal physiological conditions. It is released and activated by disintegrated platelets, and has biological activities that stimulate specific cell chemotaxis and promote specific cell growth. In addition, when tissues are damaged, macrophages, vascular smooth muscle cells, fibroblasts, endothelial cells, embryonic stem cells, etc. can also synthesize and release PDGF. When the liver is damaged, macrophages, platelets, infiltrating inflammatory cells, damaged endothelial cells, and activated hepatic stellate cells can all secrete PDGF. It works in an autocrine and paracrine manner. The bound 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 bonds.
Figure 1. Protein structure of PDGF.
Classifications and Structures
The platelet-derived growth factor family includes platelet growth factor (PDGF) and vascular endothelial cytokine (VEGF). Each growth factor can be produced by a variety of cells, and its receptors are all tyrosine kinase (RTK) type receptors. Members of the platelet-derived growth factor family include: PDGFA, PDGFB, PDGFC, PDGFD, Placental Growth Factor (PGF), and vascular endothelial growth factors VEGF, VEGF41, VEGFB, VEGFC, FIGF (VEGFD), etc. The common platelet-derived factor PDGF is a homo- or hetero-dimer formed by connecting two polypeptide chains through disulfide bonds, which makes PDGF have a variety of dimer structures, namely PDGF-AA, PDGF-BB, PDGF -AB, PDGF-CC and PDGF-DD. The molecular weight of the PDGF-A chain is 16KD, and the PDGF-B chain is 14KD. A and B chain genes are located on chromosomes 7 and 22, respectively. Generally known as PDGFI, PDGF-AA, molecular weight is 31KD, contains 7% sugar, PDGFII, PDGF-BB, molecular weight is 28KD, contains 4% sugar, both of which are composed of two highly homologous A and B chains, Monocytes / macrophages are cells that primarily synthesize PDGF.
Figure 2. Types of VEGF and their VEGF receptors.
PDGF was originally found in platelets and released from platelet alpha particles early in the injury, initiating and accelerating tissue wound repair. There are several aspects of PDGF biological activity:
Figure 3. Crystal structure of Vammin, a VEGF-F from a snake venom.
1. Chemotactic activity. Induces migration of macrophages and fibroblasts, and has chemotaxis to neutrophils, smooth muscle cells, and fibroblasts. In the early stage of trauma, it can promote the accumulation of surrounding cells to the wound site, cooperate with platelet coagulation, activate the immune system of the wound site, and lay the foundation for wound repair.
2. It has vasoconstrictive activity. PDGF can cause vasoconstriction and is a stronger vasoactive substance than angiotensin II. In the early stage of trauma, it can stimulate the rapid contraction of capillaries in the wound site, reduce blood pressure and flow velocity in the wound site, promote blood coagulation, and create conditions for wound repair. At the same time, PDGF can induce the division and proliferation of damaged epithelial cells and endothelial cells, promote the formation and regeneration of blood vessels, and provide a guarantee for wound repair.
3. Promoting mitotic effect. PDGF can stimulate the proliferation and proliferation of vascular smooth muscle cells, fibroblasts and glial cells. PDGF transfers cell signals by activating PDGF receptor transmembrane proteins, stimulating fibroblasts, glial cells, smooth muscle cells and other cells that are stagnated in G0/G1 phase to enter the division and proliferation cycle.
4, involved in phosphatase activation and prostaglandin metabolism. When PDGF interacts with cells with receptors, it can induce the phosphoinositide cycle and the release of arachidonic acid, and promote the production of prostaglandins, PGI2 and PGE2. The increase of PGI2 and PGE2 may accelerate bone resorption and increase its vasodilatory and antiplatelet activity.
A clot stops bleeding when a tissue in the body is damaged. The formation of a blood clot must not lack platelets, which accumulate at the bleeding point and form a material barrier to prevent further blood loss. At the same time, platelets release several growths factors-the most important being platelet-derived growth factor (PDGF)-which stimulates the growth of adjacent connective tissue cells. These connective tissue cells are pioneers in rebuilding damaged tissues and healing wounds. Experiments have shown that PDGF is one of the earlier growth factors in the process of wound healing. It plays an important role in the whole process of wound healing, mainly in promoting wound healing. During wound healing, PDGF can be released by a variety of cells, and PDGF is divided into three AA/AB/BB physiologically active forms. The BB type can better promote the growth of fibroblasts. Therefore, it promotes cytochemical tactile reinforcement and cell proliferation related to wound repair, strengthens the formation of granulation tissue, promotes wound healing and shortens the healing time.