title: Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.
abstract: BACKGROUND
  Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It 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.
  
  
  OBJECTIVE
  To identify biomarkers associated with AGA.
  
  
  METHODS
  Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers.
  
  
  RESULTS
  This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/β-catenin and bone morphogenic protein/transforming growth factor-β signalling 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, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss.
  
  
  CONCLUSIONS
  This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.
authors.affiliation: Inserm UMR976, Skin Research Institute, F-75475, Paris, France.|University Paris Diderot, Sorbonne Paris-Cité, Hôpital Saint-Louis, F-75475, Paris, France.
authors.forename: L
authors.identifier: http://orcid.org/0000-0002-5952-3282
authors.initials: L
authors.lastname: Michel
authors.affiliation: Centre Sabouraud, F-75475, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Reygagne
authors.affiliation: NICN UMR 7259 CNRS Faculté de Médecine, 13344, Marseille, France.|GENEX, 91160, Longjumeau, France.
authors.forename: P
authors.initials: P
authors.lastname: Benech
authors.affiliation: Inserm UMR976, Skin Research Institute, F-75475, Paris, France.|University Paris Diderot, Sorbonne Paris-Cité, Hôpital Saint-Louis, F-75475, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Jean-Louis
authors.affiliation: Laboratoire BIO-EC, 91160, Longjumeau, France.
authors.forename: S
authors.initials: S
authors.lastname: Scalvino
authors.affiliation: Inserm UMR976, Skin Research Institute, F-75475, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Ly Ka So
authors.affiliation: Centre Sabouraud, F-75475, Paris, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Hamidou
authors.affiliation: Centre Sabouraud, F-75475, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Bianovici
authors.affiliation: Plateforme de qPCR à Haut Débit Genomic Paris Centre, IBENS, 75005, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Pouch
authors.affiliation: Plateforme de qPCR à Haut Débit Genomic Paris Centre, IBENS, 75005, Paris, France.|Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, University Paris Diderot, Sorbonne Paris-Cité, CNRS, 75005, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Ducos
authors.affiliation: Inserm UMR976, Skin Research Institute, F-75475, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Inserm UMR976, Skin Research Institute, F-75475, Paris, France.|University Paris Diderot, Sorbonne Paris-Cité, Hôpital Saint-Louis, F-75475, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: GENEX, 91160, Longjumeau, France.
authors.forename: A
authors.initials: A
authors.lastname: Patatian
authors.affiliation: GENEX, 91160, Longjumeau, France.|Laboratoire BIO-EC, 91160, Longjumeau, France.
authors.forename: E
authors.initials: E
authors.lastname: Lati
authors.affiliation: ICSN, 91198, Gif-sur-Yvette, France.
authors.forename: J
authors.initials: J
authors.lastname: Wdzieczak-Bakala
authors.affiliation: Ales Groupe, 95871, Bezons, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Choulot
authors.affiliation: IEB-Lucas Meyer Cosmetics, 31520, Ramonville, France.
authors.forename: E
authors.initials: E
authors.lastname: Loing
authors.affiliation: IEB-Lucas Meyer Cosmetics, 31520, Ramonville, France.
authors.forename: M
authors.initials: M
authors.lastname: Hocquaux
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000328:Adult; D000505:Alopecia / Q000235:genetics*; D000704:Analysis of Variance; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D051177:Catenins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D008297:Male; D015398:Signal Transduction / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014807:Vitamin D / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D051177:Catenins; D018076:DNA, Complementary; D005819:Genetic Markers; D016212:Transforming Growth Factor beta; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human