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Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin.

Tong T, Kim N, Park T - PLoS ONE (2015)

Bottom Line: Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment.These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin.The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, Yonsei University, Seoul, South Korea.

ABSTRACT

Methodology and principal findings: Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression.

Conclusions and significance: These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

No MeSH data available.


Related in: MedlinePlus

Effects of cycloheximide on gene expression changes in DPCs induced by oleuropein treatment.DPCs were allowed to attach overnight and then treated (60 min) with cycloheximide (10 μg/ml) and thereafter switched to medium with or without oleuroepin (20 μM) in the presence of cycloheximide (10 μg/ml) for 24 h. mRNA expression levels of LEF1, Cyc-D1, IGF-1, HGF, VEGF, and KGF were measured by RT-PCR. A representative image of triplicate experiments is shown in the left panel. The right panel shows the intensity of the bands that were densitometrically measured and normalized against the mRNA expression level of GAPDH. The RT-PCR results are the mean ± SD from duplicates of three independent experiments. ns = P > 0.05, * = p < 0.05, ** = p < 0.01 (student’s t-test).
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pone.0129578.g008: Effects of cycloheximide on gene expression changes in DPCs induced by oleuropein treatment.DPCs were allowed to attach overnight and then treated (60 min) with cycloheximide (10 μg/ml) and thereafter switched to medium with or without oleuroepin (20 μM) in the presence of cycloheximide (10 μg/ml) for 24 h. mRNA expression levels of LEF1, Cyc-D1, IGF-1, HGF, VEGF, and KGF were measured by RT-PCR. A representative image of triplicate experiments is shown in the left panel. The right panel shows the intensity of the bands that were densitometrically measured and normalized against the mRNA expression level of GAPDH. The RT-PCR results are the mean ± SD from duplicates of three independent experiments. ns = P > 0.05, * = p < 0.05, ** = p < 0.01 (student’s t-test).

Mentions: We described here oleuroepin-induced stimulation of the Wnt/β-catenin signaling pathway both in vitro and in vivo and the upregulation of IGF-1, KGF, HGF, VEGF gene expression in mouse skin tissues. To check whether the effects of oleuroepin were due to a direct action on β-catenin accumulation and gene transcription or mediated through increased expression of oleuroepin-dependent auxiliary proteins, we analyzed the effect of oleuropein in the presence of the protein synthesis inhibitor, CHX (Fig 7). Our results showed that the accumulation of β-catenin by oleuropein, as determined by immunocytochemistry, was blocked by cycloheximide (Fig 7). The expressions of Wnt target genes, such as LEF1 and Cyc-D1, and several growth factors, including IGF-1, HGF, VEGF, and KGF, were upregulated by oleuropein within 24 h, but the effect of oleuropein was indirect since induction on these genes was abolished by CHX (Fig 8).


Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin.

Tong T, Kim N, Park T - PLoS ONE (2015)

Effects of cycloheximide on gene expression changes in DPCs induced by oleuropein treatment.DPCs were allowed to attach overnight and then treated (60 min) with cycloheximide (10 μg/ml) and thereafter switched to medium with or without oleuroepin (20 μM) in the presence of cycloheximide (10 μg/ml) for 24 h. mRNA expression levels of LEF1, Cyc-D1, IGF-1, HGF, VEGF, and KGF were measured by RT-PCR. A representative image of triplicate experiments is shown in the left panel. The right panel shows the intensity of the bands that were densitometrically measured and normalized against the mRNA expression level of GAPDH. The RT-PCR results are the mean ± SD from duplicates of three independent experiments. ns = P > 0.05, * = p < 0.05, ** = p < 0.01 (student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4462586&req=5

pone.0129578.g008: Effects of cycloheximide on gene expression changes in DPCs induced by oleuropein treatment.DPCs were allowed to attach overnight and then treated (60 min) with cycloheximide (10 μg/ml) and thereafter switched to medium with or without oleuroepin (20 μM) in the presence of cycloheximide (10 μg/ml) for 24 h. mRNA expression levels of LEF1, Cyc-D1, IGF-1, HGF, VEGF, and KGF were measured by RT-PCR. A representative image of triplicate experiments is shown in the left panel. The right panel shows the intensity of the bands that were densitometrically measured and normalized against the mRNA expression level of GAPDH. The RT-PCR results are the mean ± SD from duplicates of three independent experiments. ns = P > 0.05, * = p < 0.05, ** = p < 0.01 (student’s t-test).
Mentions: We described here oleuroepin-induced stimulation of the Wnt/β-catenin signaling pathway both in vitro and in vivo and the upregulation of IGF-1, KGF, HGF, VEGF gene expression in mouse skin tissues. To check whether the effects of oleuroepin were due to a direct action on β-catenin accumulation and gene transcription or mediated through increased expression of oleuroepin-dependent auxiliary proteins, we analyzed the effect of oleuropein in the presence of the protein synthesis inhibitor, CHX (Fig 7). Our results showed that the accumulation of β-catenin by oleuropein, as determined by immunocytochemistry, was blocked by cycloheximide (Fig 7). The expressions of Wnt target genes, such as LEF1 and Cyc-D1, and several growth factors, including IGF-1, HGF, VEGF, and KGF, were upregulated by oleuropein within 24 h, but the effect of oleuropein was indirect since induction on these genes was abolished by CHX (Fig 8).

Bottom Line: Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment.These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin.The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, Yonsei University, Seoul, South Korea.

ABSTRACT

Methodology and principal findings: Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression.

Conclusions and significance: These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

No MeSH data available.


Related in: MedlinePlus