Project description:Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet the mechanisms for decreased hair growth in this disorder are unclear. Here, we show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein-coupled receptor 44 (GPR44), but not the prostaglandin D2 receptor 1(PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization 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. 5 individuals with Androgenetic Alopecia were biopsied at both their haired and bald scalp for mRNA purification and microarray (total 10 arrays)
Project description:To identify differentially expressed genes in androgenetic alopecia specifically in the adipose, adipose tissue samples from affected male participants were collected through punch biopsy at two different sites: bald (frontal) and normal (occipital,as control) scalp. After removal of the epidermis, dermis and hair follicle, we isolated RNA from the remaining adipose layer of the bald and normal scalp then performed gene expression analysis on the RNA-seq data to compare the profiles of the bald and normal scalp.
Project description:Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet the mechanisms for decreased hair growth in this disorder are unclear. Here, we show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein-coupled receptor 44 (GPR44), but not the prostaglandin D2 receptor 1(PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization 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.
Project description:Background: The male androgenetic alopecia (AGA) is the most common form of hair loss in men and is hereditary in more than 80% of cases and characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be identified. Objectives: Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp skin vertex biopsies of hairless/bold men with premature AGA and healthy volunteers. Results: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory and immunoglobulin-associated immune mediators were significantly over-expressed in AGA. In contrast, under-expressed genes appear to be associated with the Wnt/β-catenin and BMP/TGF-β signaling pathways. Although the involvement of these pathways in hair follicle regeneration is well-described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin (POMC), as confirmed by RT-qPCR and immunohistochemistry. In addition, a lower expression of CYP27B1 in AGA patients supports that alteration of vitamin D metabolism contributes to hair loss. Conclusion: Altogether, this study provides evidence for distinct molecular events contributing to alopecia that might be targeted for new therapeutic approaches.
2017-12-13 | GSE90594 | GEO
Project description:Microbiome in the hair follicle of androgenetic alopecia patients
| PRJEB22473 | ENA
Project description:Microbiome in the hair follicle of androgenetic alopecia patients
Project description:To examined the genome-wide expression levels of lncRNAs in androgenetic alopecia tissues and paired adjacent normal tissues by microarray analysis. We identified numerous lncRNAs that were differentially regulated between androgenetic alopecia and paired normal tissues.
Project description:Autoimmune alopecia is a prevalent, highly morbid disease. The inflammatory pathways causing hair loss are not well characterized. We profiled two tissue microarrays comparing healthy skin to scarring alopecia and alopecia areata via spatial transcriptomics to analyze the genes and pathways dysregulated in autoimmune alopecia in direct proximity to the hair follicle.
Project description:Androgenetic alopecia (AGA) affects over 1.5 billion individuals, causing progressive hair loss with psychological and quality-of-life burdens. Current pharmacological treatment for AGA faces challenges due to systemic side effects from oral medications or limited efficacy of topical applications. Herein we developed a comb-shaped bioelectronic system, named “Detangle”, for efficient AGA treatment during daily hair combing. This system features electronic teeth embedded with height-differentiated electrodes and integrated drug-loading modules, which generate an enhanced electric field penetrating up to ~9 times deeper into hair follicle regions than conventional external application. The localized electric field synchronizes electro-stimulating hair follicles, and electro-delivering vascular endothelial growth factor A (VEGFA) encoding plasmid and steroid 5-alpha-reductase 2 (SRD5A2) targeting siRNA into follicular cells for promoting angiogenesis and suppressing androgen synthesis. Through these two synergistic mechanisms of cellular metabolism regulation, the system significantly increases hair restoration efficacy, improving the outcome from 70% to nearly 100% within one month compared to conventional treatment. The Detangle system proves safe and effective for deep tissue delivery in dermatology.