Human hair follicles contain two forms of ATP‐ sensitive potassium channels, only one of which is sensitive to minoxidil

Shorter, Katie; Farjo, Nilofer; Picksley, Steven M.; Randall, Valerie A.

doi:10.1096/fj.07-099424

Cited by 126 publications

(138 citation statements)

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“…In line with the postulated mode of action of minoxidil, one of the most successful therapeutic molecules for AGA, [10] we identified differentially regulated genes responsible for structure and function of cation channels.…”

Section: Letter To the Editormentioning

confidence: 89%

“…[9] The subsequent analysis of the m 6 A methylation status of the RNA gave first hints towards higher methylation in AGA-affected sites ( Figure S2). In line with the postulated mode of action of minoxidil, one of the most successful therapeutic molecules for AGA, [10] we identified differentially regulated genes responsible for structure and function of cation channels.[11] Three AGA-downregulated ion channel markers (LRRC26, KCNK5, and B3GNT3) detected, to date, have not been described in hair follicles. …”

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confidence: 99%

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Infundibular protein and RNA microarray analyses from affected and clinically non‐affected scalp in male androgenetic alopecia patients

Vogt

Pfannes

Fimmel

et al. 2017

Experimental Dermatology

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Non-invasive sample collection methods could facilitate clinical research on hair diseases. In an exploratory experimental study on six male volunteers with untreated androgenetic alopecia (AGA), Hamilton-Norwood stage IIIv-IV, skin surface and infundibular protein as well as RNA extracts from plucked hair follicles were analyzed from frontal skin, vertex and clinically unaffected occiput. Slightly increased levels of inflammatory markers were only found in AGAaffected scalp skin and infundibulum, not in RNA from plucked hair follicles. RNA expression profiles point towards differential expression of genes involved in hair cycle regulation, hair keratin production, but also RNA methylation and ion channel regulation. | BACKGROUNDOur current concept of androgenetic alopecia (AGA) suggests that different factors including hormonal effects, ion channel regulation, vascularization, and prostaglandins contribute to the disease onset and progression. [1][2][3] Microinflammation has been postulated to be involved. [4,5] Yet, exploratory molecular work in patients is difficult.Clinical trials largely rely on macroscopic readouts. Inclusion of biomarkers usually requires skin biopsies, limiting the number of investigational sites and frequency of sampling. Non-invasive sample collection methods could help increase our understanding of hair growth regulation. | QUESTIONS ADDRESSEDIn this pilot study, we combined clinical diagnostics with a new method for non-invasive sampling of infundibular protein [6] and RNA microarray analysis of plucked hair follicles to investigate inflammatory processes in AGA-affected scalp skin. Additionally, we looked into gene expression to identify new markers of relevance in androgenetic alopecia. | EXPERIMENTAL DESIGNSix male volunteers with untreated AGA, Hamilton-Norwood stage IIIv-IV, were included. Investigational sites (frontotemporal area, vertex, clinically unaffected occiput) were assessed (Table S1) by phototrichogram analysis, sebum and pH determination, optical coherence tomography (OCT), ultrasonography, hair root plucking (trichogram, Figure S1) and mini-zone cyanoacrylate skin surface stripping (CSSS).[6] Seborrhoeic dermatitis was an exclusion criterion.RNA from about 30 hairs from each site was obtained by hair plucking and extraction performed using RNeasy kit (Qiagen, Hilden, Germany). For hybridization, Agilent Gene Expression Hybridization kit (Agilent Technologies Inc., Santa Clara, CA, USA) was used, andCy3-labelled fragmented cRNA hybridized overnight to Agilent WholeHuman Genome Oligo Microarrays 8 × 60 K V2 using Agilent's recommended hybridization chamber and oven. The Agilent FeatureExtraction software was used to read out and process the microarray image files. Data were normalized followed by correlation analysis and differential gene expression analysis (DGA). For further details concerning study plan, methods and the microarray data, please refer to the Appendix S1. | RESULTSConsistent with the clinical diagnosis, the total hair density was significantl...

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Section: Letter To the Editormentioning

confidence: 89%

mentioning

confidence: 99%

Infundibular protein and RNA microarray analyses from affected and clinically non‐affected scalp in male androgenetic alopecia patients

Vogt

Pfannes

Fimmel

et al. 2017

Experimental Dermatology

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“…To identify new hair-growing agents, cultures of hair fol- licles from several species such as human, 11,32) rat, 39) sheep 51) and mouse 40,52) were developed. The hair follicle culture method has several advantages in hair research, including the measure of hair-fiber elongation and maintenance of normal architecture.…”

Section: Discussionmentioning

confidence: 99%

“…The action mechanisms of minoxidil on hair growth include the increase of ATP-sensitive K + -channel opening, the upregulation of vascular endothelial growth factor (VEGF) and the activation of the β-catenin pathway in dermal papilla cells (DPCs). [11][12][13] However, because of unwanted side effects and transient action, dissatisfied responses to finasteride and minoxidil in alopecia have been reported. 14,15) Therefore, the demand for new therapies for alopecia is on the rise.…”

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confidence: 99%

Promotion Effect of Apo-9′-fucoxanthinone from <i>Sargassum muticum</i> on Hair Growth <i>via</i> the Activation of Wnt/β-Catenin and VEGF-R2

Kang

Yoo

Hyun

et al. 2016

Biological & Pharmaceutical Bulletin

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This study was conducted to evaluate the effects of Sargassum muticum extract and apo-9′-fucoxanthinone, a principal component of S. muticum, on hair growth. When rat vibrissa follicles were treated with S. muticum extract for 21 d, the hair-fiber lengths for the vibrissa follicles increased significantly. Treatment with the S. muticum extract and the EtOAc fraction of the S. muticum extract markedly increased the proliferation of dermal papilla cells (DPCs) and decreased the 5α-reductase activity. In addition, the EtOAc fraction of the S. muticum extract significantly promoted anagen initiation in C57BL/6 mice. Especially, apo-9′-fucoxanthinone, an active constituent from the S. muticum extract, caused an increase in DPC proliferation and a decrease in 5α-reductase activity. To elucidate the molecular mechanisms of apo-9′-fucoxanthinone on the proliferation of DPCs, we examined the level of various signaling proteins. Apo-9′-fucoxanthinone increased the level of vascular endothelial growth factor receptor-2 (VEGF-R2), Wnt/β-catenin signaling proteins such as phospho(ser9)-glycogen synthase kinase-3β (GSK-3β) and phospho(ser552)-β-catenin, whereas apo-9′-fucoxanthinone did not affect the transforming growth factor-β (TGF-β) signaling proteins such as Smad2/3. These results suggest that apo-9′-fucoxanthinone from S. muticum could have the potential for hair growth with DPC proliferation via the activation of Wnt/β-catenin signaling and the VEGF-R2 pathway.

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“…Uptake and conversion of minoxidil to minoxidil sulfate occurs within the HF, suggesting a direct action on the follicle [134]. The most probable site of action of minoxidil is the DP [135], and the mechanism of action has been linked to its effects on the Kir6.1/SUR2B potassium channel expressed by the derma papilla [136][137][138].…”

Section: Treatments Of Hair Growth Disorders: Room For Improvementmentioning

confidence: 99%

Biology of Human Hair: Know Your Hair to Control It

Araújo

Fernandes

Cavaco‐Paulo

et al. 2010

Advances in Biochemical Engineering/Biotechnology

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Hair can be engineered at different levels-its structure and surfacethrough modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization.

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Human hair follicles contain two forms of ATP‐ sensitive potassium channels, only one of which is sensitive to minoxidil

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Cited by 126 publications

References 62 publications

Infundibular protein and RNA microarray analyses from affected and clinically non‐affected scalp in male androgenetic alopecia patients

Infundibular protein and RNA microarray analyses from affected and clinically non‐affected scalp in male androgenetic alopecia patients

Promotion Effect of Apo-9′-fucoxanthinone from <i>Sargassum muticum</i> on Hair Growth <i>via</i> the Activation of Wnt/β-Catenin and VEGF-R2

Biology of Human Hair: Know Your Hair to Control It

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