Thymosin Beta 4 Increases Hair Growth by Activating Hair Follicle Stem Cells.
"Thymosin β4, a ubiquitous 4.9‐kDa polypeptide originally isolated from bovine thymus, is a potent mediator of cell migration and differentiation. It was identified as a gene up‐ regulated four‐ to sixfold during early endothelial cell tube formation and found to promote angiogenesis. It is present in wound fluid, and when added topically or given systemically, it promotes angiogenesis and wound healing. Thymosin β4 elicits cell migration through a specific interaction with actin. In angiogenesis and in wound healing, thymosin β4 acts by accelerating the migration of endothelial cells and keratinocytes and increasing the production of extracellular matrix‐degrading enzymes.""Thymosin β4 promotes hair growth in normal rats and mice. A specific subset of follicular keratinocytes in the mouse skin, which originates at the bulge region, expresses thymosin β4. The temporal and spatial distribution of these keratinocytes parallel the pattern reported for the stem cells and their daughter TA cells at the different stages of the hair cycle (9, 10). We isolated clonogenic keratinocytes from the bulge compartment of the rat vibrissa follicle, further characterized them as an immediate progeny of the stem cells, and found that these cells express high levels of thymosin β4 when cultured in vitro. We show that thymosin β4 promotes hair clonogenic keratinocyte cell migration, as well as secretion of the extracellular matrix‐degrading enzyme matrix metalloproteinase 2 (MMP‐2)."
"Thus, thymosin β4 accelerates hair growth, in part, due to its effect on critical events in the active phase of the hair follicle cycle, including promoting the migration of stem cells and their immediate progeny to the base of the follicle, differentiation, and extracellular matrix remodeling."
"Taken together, our results suggest that in addition to its known angiogenic and wound healing effects, thymosin β4 is a naturally occurring modulator of hair growth that acts by stimulation of stem cell migration, protease production, and differentiation."
"While studying wound healing in rat skin, we unexpectedly observed visually and at the histological level increased hair growth at the wound margins 7 days after topical treatment with thymosin β4 (unpublished observation). In this study, we have shaved the skin of healthy rats and applied thymosin β4 topically on one side of the shaved area and the control vehicle on the opposing lateral side of the same animal. After 7 days of treatment, we observed an increased number of anagen‐phase hair follicles in the skin areas treated with thymosin β4 (Fig. 1a and d). The number of anagen follicles was approximately twofold greater than in rats treated with vehicle alone. The increased number of hairs in anagen phase was retained with continued tri‐ weekly treatment over 30 days. Within 14 days of treatment cessation, the number of active hair follicles decreased to control levels. We next tested whether thymosin β4 would promote hair growth in 8‐wk‐old C57BL6 wild‐type mice. Animals used in this experiment have all of their hair follicles in the telogen stage as judged by their pink skin color. The mice were shaved and thymosin β4 was applied topically on the shaved area as described in Methods. Control animals were treated with vehicle alone. As shown in Fig. 1c and ƒ, thymosin β4‐treated (but not control) animals displayed quick hair regrowth. Histological examination confirmed the thymosin β4‐induced activation of the hair follicles (Fig. 1b and e)."
"Hair growth acceleration by thymosin β4 may also be attributed, in addition to its effects on stem cells, to pro‐angiogenic and other previously described biological activities of this molecule. It was recently reported that VEGF promotes hair follicle development, presumably due to its angiogenic activity. Thymosin β4 is angiogenic, like VEGF, and the activity of thymosin β4 may, in addition to its effects on stem cells, be due to its angiogenic activity. Recently, another angiogenic molecule, hepatocyte growth factor, has been identified in hair follicles and found to promote hair growth. Hepatocyte growth factor up‐regulates thymosin β4 expression and may be acting by increasing thymosin β4 and/or synergizing with it. Furthermore, steroids have been used successfully to treat certain types of hair loss. Thymosin β4 is the anti‐inflammatory molecule identified as increased in steroid‐treated monocytes. Thus, treatment with steroids may also involve the activity of thymosin β4 on the hair growth." (1)
Thymosin β4 Creates Blood Vessels Near Hair Follicles.
"By depilation and histological examination of the skin, we confirmed the effect of Tβ4 on hair growth, the number of hair shafts and hair follicle (HF) structure... Changes in the expression of β-catenin and Lef-1, the two key molecules in the Wnt signaling pathway, were similar to the changes observed in Tβ4 expression. We also found that compared to the control mice, the mRNA and protein expression of MMP-2 and VEGF were increased in the Tβ4 over-expressing mice, while the level of E-cadherin (E-cad) remained the same... Based on the above results, we believe that Tβ4 may regulate the levels of VEGF and MMP-2 via the Wnt/β-catenin/Lef-1 signaling pathway to influence the growth of blood vessels around HFs and to activate cell migration."
Thymosin βeta 4 Plays an Important Role in Hair Follicle Development and Hair Growth.
"Mechanistically, it has been shown that Tβ4 accelerates angiogenesis by increasing vascular endothelial growth factor (VEGF) expression, which may be secondary to the effects of Tβ4 on MAPK, PKC and WNT signaling. Thus, we also explored the relationship between Tβ4 and VEGF expression in the skin, and dissected the underlying signaling pathways associated with this effect... The downstream mechanism of Tβ4 signaling on VEGF and how it regulates hair growth and development is unknown. VEGF is also known as the vascular permeability factor, and plays a key role of angiopoiesis and micro-vascular permeability, acting through transmembrane protein receptors in endothelial cells and other cells to regulate transmembrane signal transduction. One of the receptors that VEGF binds to is VEGFr-2. Previously, VEGF165 was shown to increase the phosphorylation of ERK, C-JUN and P38 via VEGFr-2 and thereby induced angiogenesis and HF development in humans. It has also been shown that VEGF induces the proliferation of vascular endothelial cells via ERK1/2 and P38."
"WT, KTP and KO mice were depilated at approximately weeks 8–10 of age. Eleven days after depilation, we observed that the hair of KTP mice was longer and thicker than that of WT mice, whereas the depilated skin of KO mice became black without hair growth. If the speed of hair re-growth in WT mice was considered to be normal, then KTP mice had faster hair growth, whereas this process was much slower in KO mice." (3)
"Relative to WT mice, Tβ4 mRNA expression was 5.65 times higher in KTP mice."
"By observing hair re-growth, we found that it was required 13 days in WT mice, 11 days in KTP mice and 16 days in KO mice to reach the same extent." (3)
Thymosin β4 Increases Speed of Hair Growth After Shaving
"The effect of thymosin β4 on hair growth was analyzed in the transgenic mice. We watched the hair growth pattern of transgenic mice after birth but could not detect any differences in the onset of hair growth when compared with the wild type mice. However, we found significant difference in the speed of hair re-growth after shaving." (4)
