Growth factors stimulate keratinocytes to differentiate, proliferate, and migrate to different layers of the skin. Epidermal, fibroblast, and hepatocyte growth factor (HGF) families as well as insulin-like growth factor enhance keratinocyte growth. In turn, keratinocytes secrete many factors, such as granulocyte- macrophage colony stimulating growth factor (G-CSF), platelet derived growth factor (PGDF), VEGF, and pro-inflammatory interleukins, including IL-6 and IL-8 to modulate cell migration to skin and regulate their microenvironment. TGFα, which stimulates fibrillogenesis in fibroblasts, is part of the epidermal growth factor family and is also secreted by keratinocytes. 

Mode of action

TGFβ suppresses keratinocyte growth, but like TGFα it is a powerful inducer of migration in these cells. Bone morphogenic protein also induces keratinocyte proliferation and migration in human skin. A recent study showed how topical basic fibroblast growth factor (bFGF) promotes skin barrier recovery in mice, resulting in less transepithelial water loss and keratinocyte proliferation. Its effects are amplified during the absence of other growth factors that downregulate FGF receptors, such as EGF. Moreover, topical recombinant human EGF accelerated wound healing and skin collagen deposition in rats.

Growth factors also directly affect enzymes that synthesize GAGs such as hyaluronan. EGF upregulates and TGFβ downregulates hyaluronan synthases 2 and 3 in keratinocytes. These characteristics of EGF and TGFβ have been linked to the ability of EGF to promote keratinocyte proliferation, versus the anti-proliferative but pro-differentation effects of TGFβ on keratinocytes.

Clinical Study

Several combinations of these cytokines, chemokines, and growth factors have been used as topical anti-aging agents. Cell rejuvenation serum (CRS) contains TGFβ encapsulated by liposomes, ascorbic acid, and Cimicifuga racemosa extract in a silicone base. Another cream, called TNS, contains VEGF, PDGF, G-CSF, HGF, IL-6, and IL-8 in addition to TGFβ. In one study, the specific contributions of TGFβ were analyzed by comparing CRS to CRS cream without any growth factors. Patients treated with CRS containing TGFβ had significant improvements in wrinkles, nearly 15% more compared to cream without it. TNS and CNS comparison in a clinical trial revealed that both creams produced comparable and significant improvement in wrinkles. TNS by itself was found to provide maximal benefits in the periorbital area and result in epidermal thickening. PSP is a different cream containing processed skin proteins, proprietary growth factor, and cytokines extracted from cultured first trimester fetal human dermal fibroblasts. Anti-aging effects of PSP cream showed dramatic anti-aging improvements in the periorbital and chin wrinkles in one trial. Another trial showed reduced dark circles, firmness, and improved texture in addition to decreased periorbital wrinkles as a result of the PSP cream, but not significantly.