Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells

Abstract

The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed. This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA. Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation. These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.

Visible-to-Near IR Quantum Dot–Based Hypermulticolor High-Content Screening of Herbal Medicines for the Efficacy Monitoring of Hair Growth Promotion and Hair Loss Inhibition

“…Kwack et al 27 found that the phosphorylation of GSK3β, PKA, and PKB and expression of Axin2, Lef-1, and EP2 were accelerated by minoxidil in HFDPC. Lachgar et al 28 demonstrated that minoxidil in the range of 0.2 to 12 µM raised VEGF mRNA expression and protein in HFDPC. Previously, no concrete molecular evidence existed that minoxidil directly affects the upregulation/downregulation of DKK-1, IGF-1, TGF-β2, and Wnt5α.…”

Androgenetic Alopecia: a Review and Emerging Treatments

“…An VEGF mRNA is strongly expressed in DP cells during anagen phase with a substantial decrease of expression during catagen and telogen phases Topical minoxidil on the hair follicle can increased the expression of VEGF mRNA, presented in the DP cells [49,73,74].…”

“…Lachgar, et al [73] performed a study to evaluate if minoxidil could affect the expression of VEGF. According to the authors, minoxidil caused an elevation of VEGF and should be consider an indirect inducer of angiogenesis through an up regulation of the expression of VEGF in DP cells, during the anagen phase.…”

Addressing Androgenetic Alopecia-A Complex Disorder-with a Multilateral Treatment Strategy

“…17,20 Ketoconazole topical treatment was observed to promote hair growth by increasing density and size of anagen follicles when used over period of 21 weeks at a concentration of 2% in a shampoo formulation. Though anti-DHT activities of ketoconazole have been reported, the major beneficial effects were suggested to be arising from its inhibitory actions on inflammation and fungal infections in the scalp.…”

“…Minoxidil is also reported to promote angiogenesis by enhancing VEGF mRNA expression in dermal papilla. 20 In in vitro settings, minoxidil stimulates PGE2 and leukotriene B4 expression, and block prostacyclin production in by dermal papilla cells. Also the expression of EP2, one of the PGE2 receptors responsible for lengthening of anagen phase is amplified under the influence of minoxidil treatment.…”