Oligonucleotide treatment increases eumelanogenesis, hair pigmentation and melanocortin-1 receptor expression in the hair follicle.
It was previously reported that telomere homologue oligonucleotides (T-oligos) can induce a variety of cellular responses in skin including increased melanogenesis. To assess the effects of T-oligos on hair pigmentation, we administered thymidine dinucleotide (pTT), one-third of the TTAGGG telomere repeat sequence, intradermally at distinct time points of the depilation-induced hair cycle in C3H/HeJ mice. Penetration of T-oligos into the hair follicle (HF) was monitored by using FITC-labelled pTT and confocal microscopy. pTT treatment on days 1-5 after depilation, during early anagen, did not significantly alter the number and proliferation of melanocytes (Trp-2-positive cells), compared with vehicle-treated controls. However, pTT treatment on days 5-12 after depilation, during mid- to late anagen, resulted in the formation of darker hairs, that showed a significantly increased eumelanin/total melanin ratio in their sub-apical agouti band region, compared with vehicle-treated controls (P < 0.05). By RT-PCR and western blot, full thickness skin of pTT-treated mice showed increases in Trp-1, Trp-2 and tyrosinase mRNA and protein levels, compared with control mice. Western blot analyses of two receptors that positively regulate eumelanogenesis, melanocortin type 1 receptor (MC-1R) and kit, showed increased expression of MC-1R protein in pTT-treated versus control skin, while the levels of c-kit receptor remained unchanged. These data demonstrate that pTT treatment increases eumelanogenesis in HFs, associated with increased tyrosinase, TRP-1 and MC-1R expression. These data also raise the possibility of using T-oligos to modulate hair pigmentation.
Atoyan
Ruzanna Y
RY
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
Sharov
Andrey A
AA
Eller
Mark S
MS
Sargsyan
Aram
A
Botchkarev
Vladimir A
VA
Gilchrest
Barbara A
BA
D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006200:Hair Color / Q000502:physiology*; D018859:Hair Follicle / Q000502:physiology*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009841:Oligonucleotides / Q000493:pharmacokinetics*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010858:Pigmentation / Q000502:physiology*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013936:Thymidine
D015226:Dinucleoside Phosphates; D008543:Melanins; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D044102:Receptor, Melanocortin, Type 1; C017758:thymidylyl-(3'-5')-thymidine; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D013936:Thymidine