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
| PRJEB22475 | 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:Scarring alopecia consists of a collection of disorders characterized by destruction of hair follicles, replacement with fibrous scar tissue, and irreversible hair loss. Alopecia affects men and women worldwide and can be a significant source of psychological stress and depression for affected individuals. The purpose of this study was to explore metabolic profiles in scalp tissue samples from normal control subjects (n=6) and in matched samples obtained from affected (n=12) and unaffected (n=12) areas of the scalp in patients with lymphocytic Frontal Fibrosing Alopecia (FFA). Frontal fibrosing alopecia results from destruction of hair follicles by an inflammatory lymphocytic infiltrate that is localized around the upper portion of the hair follicle.
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.