Function of basic fibroblast growth factor in skin

2018-08-18

Introduction 

Basic Fibroblast Growth Factor, Human, called basic fibroblast growth factor (bFGF/FGF-b/FGF-2), is a single chain polypeptide belonging to the heparin-binding growth factor family. It is synthesized mainly by stromal fibroblasts and functions in both an autocrine and paracrine fashion and has been shown to accelerate wound closure of patellar tendons, and believed to be the result of increased fibroblast and mesoderm cells proliferation. It is also known to be involved in cell migration and angiogenesis (new blood vessel formation) and inhibition of apoptosis, and can be used in wound healing as a cosmeceutical. bFGF has shown some promising results, the cost of multiple cytokines and their delivery, and the suboptimal endothelial migration in large tissue grafts have garnered much attention of the researchers.

Mechanism of proliferation and differentiation

bFGF signals through four receptor tyrosine kinases (FGF receptor 1 through FGF receptor (FGFR) 4) and acts in a variety of developmental processes. Studies confirmed that heparin has been demonstrated to be crucial in the interaction of bFGF and FGF receptors. It has been demonstrated that bFGF binding to FGFRs can be inhibited and facilitated by heparin in a concentration-dependent manner, that is to say higher concentrations inhibited binding whereas low concentrations facilitated the binding.

bFGF is a potent mitogen, not only for fibroblasts, but also for a variety of cells of mesodermal and neuroectodermal origin. In vitro, exogenously administered bFGF exerts mitogenic and differentiative effects on embryonic hippocampal neurons in culture, stimulates proliferation of cortical precursor cells, and (with other growth factors) regulates the generation of neurons and astrocytes from progenitor cells. It also favors the differentiation of cultured neonatal dentate granule cells. Different concentrations of bFGF may influence the fate of early cortical stem cells: low bFGF levels predominantly lead to development into neurons, whereas higher levels lead to generation into glia as well as neurons. Similar effects have been observed in vivo. Injection of an antibody against bFGF in the neonatal rat brain inhibits neurogenesis; conversely, a single subcutaneous bFGF injection in neonatal rats elicits a significant increase in hippocampal cell number. The mitotic effects of exogenous bFGF persist in the adult brain in the regions (subgranular zone of the dentate gyrus and subventricolar zone) where neurogenesis persists during adulthood. In addition, a low dose of bFGF stimulated greater increase in mRNA expression of extracellular matrix (ECM) proteins, such as collagen I and III.

But, a significantly important thing that we should pay attention to is that the bFGF could lose its biological activity rapidly when its free form is injected in vivo or in normal physiological conditions without stabilization.

Effect and application

bFGF is a repairing factor for skin and mostly acts on deep tissues and muscle tissues, which can stimulate the differentiation and division of basal collagen fibers, elastic fibers, fibroblasts to form colloid protein, enhancing the development of vascular cells in the basal layer, making the skin more elastic, reducing the lines and wrinkles, and promoting the rapid repair of defective skin. In addition, It can also induce a series of reactions of tissue repair cells, such as dermal cells, fibroblasts, capillaries, nerve endings and muscles, and it stimulates proliferation of fibroblast, regeneration and migration (controlled by the conventional fibroblast growth factor (FGF) receptor pathways) of capillary, synthesis of DNA in cell and wounds. Re-epithelialization accelerates the repair and regeneration of the wound after some complex physiological metabolism, so it can promote the formation of epidermal cells, improve the healing speed of wound surface and reduce the formation of scars on the skin. Here, the bFGF can be added into the anti-wrinkle and skin repair products in the cosmetic filed as an active ingredient to activate the metabolism of cells, promote the synthesis of collagen fibers and have a positive effect of anti-wrinkle, to rebuild the subcutaneous nerve and blood circulation tissue and enhance the effect of repairing.

References:

1. Awan B, Turkov D, Schumacher C, Jacobo A, McEnerney A, Ramsey A, Xu G, Park D, Kalomoiris S, Yao W, Jao L, Allende M, Lebrilla C and Fierro F. FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins. Stem Cell Reports. 2018, 11: 1-9.

2. Tanaka A, Nakamura H, Tabata Y, Fujimori Y, Kumasawa K and Kimura T. Kimura. J. Obstet. Gynaecol. Res. 2018.

3. Schmidt A, Ladage D, Schinköthe T, Klausmann U, Ulrichs C, Klinz FJ, Brixius K, Arnhold S, Desai B, Mehlhorn U, Schwinger RHG, Staib P, Addicks K and Bloch W. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells, 2010, 24(7): 1750-1758.

4. Zhang X, Kang X, Jin LJ, Bai J, Liu W and Wang Z. Wang. stimulation of wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF). International Journal of Nanomedicine. 2018, 13: 3897–3906.

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