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Τετάρτη 12 Απριλίου 2017

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signaling pathways

Abstract

Background

Male androgenetic alopecia (AGA) is the most common form of hair loss in men and is 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 defined.

Objectives

Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless/bald 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 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, lower expression of CYP27B1 in AGA subjects supports the notion that changes in vitamin D metabolism contributes to hair loss.

Conclusion

This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave way for new therapeutic approaches.

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