Cytokines And Growth Factors Proteins

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 Cytokines And Growth Factors Proteins Background

Growth factors are a group of cytokines, containing members like Transforming Growth Factor β-1 (TGFβ-1), Insulin-like Growth Factor I (IGF-I), Bone Morphogenic Protein 2 (BMP-2), Bone Morphogenic Protein 7 (BMP-7), and Fibroblastic Growth Factor 2 (FGF-2). TGF-β and IGF-I have been shown to stimulate the production of proteoglycans (anabolic). Additionally, IGF-I has been shown to increase chondrocyte proliferation (mitogenic). BMP-2 and BMP-7 have been shown to enhance proteoglycan synthesis, and it has been indicated that BMP-7 maybe also increase the synthesis of hyaluronic acid and its receptor CD44. FGF-2 can help the regenerative capacity of chondrocytes, as it will stimulate proliferation and redifferentiation once the chondrocytes are moved from monolayer culture to a 3D culture in a scaffold. Moreover, studies by the Loeser laboratory have shown that growth factors IGF-I and TGF-β1 when added exogenously to the culture medium can enhance the expression of certain integrins, increasing the adhesivity of the cells to the matrix; however, TGF-β1 had the opposite effect on the α1β1 integrin, decreasing chondrocyte affinity to collagen VI.
Growth factors play important roles in both positively and negatively regulating proliferation of a variety of cell types in tissue growth, differentiation, and tumorigenesis. It is thought that growth factors have an important central function in mitosis and cell differentiation because growth factors have been found in the three trophoblastic forms in immunohistochemical analyses. Moreover, an autocrine and paracrine function has been suggested in the regulation of the implantation of the blastocyst, owing to the presence of common receptors found in the human endometrium, decidual and implantation zones. Growth factors have a physiological role in fetal growth.
It is also thought that many growth factors (e.g., EGF, keratinocyte growth factor (KGF), TGF-α, TGF-β, interleukin-1, the fibroblast growth factor family, platelet-derived growth factor, and insulin-like growth factors) are involved during different stages of wound repair by regulating the synthesis of specific proteins involved in different stages of epithelial proliferation and differentiation.

Epidermal growth factor (EGF) plays an important role in cell proliferation of a variety of cells types by binding to the EGF receptor (EGFR), which stimulates several signal transduction pathways leading to the transcriptional activation of a number of growth-related genes and transcription factors including c-fos, c-jun, and Ets. This signaling pathway activation also plays an important role in the development of many solid tumors. 
Fibroblast growth factor 2 (FGF2), also known as basic fibroblast growth factor (bFGF) is expressed in the embryonic central nervous system (CNS) and it may be one of the main regulators of CNS development. It has mitogenic action on cortical progenitor cells and it also regulates the generation of neurons and glia.
Insulin-like growth factor (IGF) is associated with cell development, lifespan, and aggressiveness of various tumor types. Studies have shown that IGF-1 stimulates telomerase activity, hTERT mRNA transcription, and protein expression in androgen-dependent and independent prostate cancer cell lines. IGF-binding protein 2 (IGFBP-2) also stimulates telomerase activity in prostate cancer cells even though it acts as a growth inhibitor in normal prostate epithelial cells.
Nerve growth factor (NGF) appears to be involved in the control of epithelial cell growth and differentiation. Studies have shown that during NGF induction of cell proliferation in pheochromocytoma cells and prostate cancer cells, telomerase was significantly downregulated through the MAP kinase pathway.
The TGF-α and TGF-β families of growth factors have been implicated in the process of transformation and in the maintenance of growth of tumor cells, in association with both paracrine and autocrine mechanisms. TGF-α is structurally and functionally related to EGF, binding to the EGF-receptor and in many cases being more potent than EGF. The TGF-β superfamily is composed of three other major sub-families: the Mullerian inhibitory substance (MIS) family, the inhibin/activin family, and the TGF-β family. 
The Bone Morphogenetic Protein (BMP) family of secreted signaling molecules directs the development of multiple organs and tissue types at various stages in embryogenesis, and is implicated in congenital and adult diseases. BMP proteins belong to TGF-β superfamily. These proteins are known to stimulate bone development in vivo. These proteins are released after trauma and are likely to have an effect on bone remodeling and possibly be a connection between bone formation and resorption.

Related literatures
1. Hernandez‐Valencia M, Zarate A, Ochoa R, et al. Insulin‐like growth factor I, epidermal growth factor and transforming growth factor beta expression and their association with intrauterine fetal growth retardation, such as development during human pregnancy[J]. Diabetes, Obesity and Metabolism, 2001, 3(6): 457-462.
2. Gibbs S, Silva Pinto A N, Murli S, et al. Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation[J]. Wound Repair and Regeneration, 2000, 8(3): 192-203.