Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell FunctionsReportar como inadecuado




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Background

Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle HF is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown.

Methods and Findings

We have studied the effects of the prototypic polyamine, spermidine 0.1–1 µM, on human scalp HFs and human HF epithelial stem cells in serum-free organ culture. Under these conditions, spermidine promoted hair shaft elongation and prolonged hair growth anagen. Spermidine also upregulated expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity in situ and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells in vitro. Inhibiting the rate-limiting enzyme of polyamine synthesis, ornithine decarboyxlase ODC, downregulated intrafollicular K15 expression. In primary human epidermal keratinocytes, spermidine slightly promoted entry into the S-G2-M phases of the cell cycle. By microarray analysis of human HF mRNA extracts, spermidine upregulated several key target genes implicated e.g. in the control of cell adherence and migration POP3, or endoplasmic reticulum and mitochondrial functions SYVN1, NACA and SLC25A3. Excess spermidine may restrict further intrafollicular polyamine synthesis by inhibiting ODC gene and protein expression in the HF-s companion layer in situ.

Conclusions

These physiologically and clinically relevant data provide the first direct evidence that spermidine is a potent stimulator of human hair growth and a previously unknown modulator of human epithelial stem cell biology.



Autor: Yuval Ramot , Stephan Tiede , Tamás Bíró, Mohd Hilmi Abu Bakar, Koji Sugawara, Michael P. Philpott, Wesley Harrison, Marko Pie

Fuente: http://plos.srce.hr/



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