Dr George Cotsarelis: Advances in Understanding Androgenetic Alopecia скачать в хорошем качестве

Dr George Cotsarelis: Advances in Understanding Androgenetic Alopecia

Presented at the 8th World Congress for Hair Research (2014) in Jeju Island, South Korea. Abstract Summary: We originally localised hair follicle stem cells to the mouse and hair follicle bulge. Much progress has been made in our understanding of mouse bulge cells, but the relevance of this information to human hair follicle biology is not often studied. So, we evaluated the status of hair follicle stem cells in Androgenetic Alopecia. We analysed bald and non-bald scalp from men with Androgenetic Alopecia (AGA) for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin 15 (KRT15), CD200, CD34, and alpha-6 Integrin (ITGA6) were quantified via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small size and quiescence. These KRT15hi stem cells were maintained in bald scalp samples. However, CD200hi/ITGA6hi and CD34hi cell populations - which both possessed a progenitor phenotype, in that they localised closelyto the stem cell-rich bulge area but were larger and more proliferative than the KRT15hi stem cells - were marked diminished. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA. We then showed that prostaglandin D2 Synthase (PTGDS) is elevated at the mRNA and protein levels in balding scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor (GPR44). Furthermore, we find that a transgenic mouse, K14-Ptgs2, demonstrates elevated levels of PGD2 in skin and develops alopecia, follicular miniturisation, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.