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LXR mediated-signalling protects human hair follicles against doxorubicin-induced toxicity ex vivo

ABSTRACT: LXR mediated-signalling protects human hair follicles against doxorubicin-induced toxicity ex vivo

PROVIDER: PRJEB39421 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR4346480_1.fastq.gz	Fastqsanger.gz
	ERR4346480_2.fastq.gz	Fastqsanger.gz
	ERR4346481_1.fastq.gz	Fastqsanger.gz
	ERR4346481_2.fastq.gz	Fastqsanger.gz
	ERR4346482_1.fastq.gz	Fastqsanger.gz

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LXR mediated-signalling protects human hair follicles against doxorubicin-induced toxicity ex vivo

Project description:Although chemotherapy-induced alopecia (CIA) is one of the most distressing adverse effects of cancer treatment, there are still no pharmacological interventions available and there remains an urgent unmet need to identify novel targets for therapy. We hypothesized that selected compounds which enhance ABC transporter activity and thus drug efflux from CIA-affected hair follicle (HF) epithelium may award relative protection from chemotherapy-induced HF toxicity. We found that the LXR agonist T0901317 significantly increased cell survival, attenuated LDH release, caspase-3 activity and DNA double strand breaks (DSBs) in doxorubicin (DOX)-treated outer root sheath keratinocytes (ORS-KCs) in vitro and protected human HFs from DOX-induced apoptosis ex vivo. RNA sequencing was performed to investigate the potential mechanism(s) by which T0901317 may protect against DOX-induced cell survival and apoptosis of ORS-KC.

2021-02-19 | E-MTAB-9362 | biostudies-arrayexpress

Expression data from human hair follicle after doxorubicin treatment

2014-05-01 | GSE51484 | GEO

Expression data from human hair follicle after doxorubicin treatment

Project description:Chemotheraputic drugs are able to affect both neoplastic and normal rapidly proliferating cells. We used microarray analysis to identify molecular signatures of the early phase in the response of human hair follicles to chemotheraputic drug, doxorubicin. Human hair follicles were cultured in Williams E medium and were treated with 1 uM Doxorubicin HCl or vehicle control solution for 1 hour. 3 hours after treatmnet hair bulbs were disected for RNA isolation and RNA was analysed using Affymetrix Human Genome U133A 2.0 array. processing 3 hours after completion of the DXR treatment. Total RNA was isolated from the hair follicle bulbs using TriIzol® Reagent (Invitrogen, San Diego, CA). All experiments were performed using at least three replicates, and RNA isolated from three experimental and control samples was pooled and processed for microarray analyses using one sample of pooled RNA per experimental and control group.

2014-05-01 | E-GEOD-51484 | biostudies-arrayexpress

Hair follicles modulate skin barrier function

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Expression data from human hair follicles (ex vivo) incubated with cyclosporine A and vehicle control

Project description:Since hair growth disorders can carry a major psychological burden, more effective human hair growth-modulatory agents need to be urgently developed. Here, we used the hypertrichosis-inducing immunosuppressant, cyclosporine A (CsA), as a lead compound to identify new hair growth-promoting targets. Through microarray analysis we identified the Wnt inhibitor, SFRP1, as being downregulated in the dermal papilla (DP) of CsA-treated human scalp hair follicles (HFs) ex vivo. Therefore, we further investigated the function of SFRP1 using a pharmacological approach and found that SFRP1 regulates intrafollicular canonical Wnt/β-catenin activity through inhibition of Wnt ligands in the human hair bulb. Conversely, inhibiting SFRP1 activity through the SFRP1 antagonist, WAY-316606, enhanced hair shaft production, hair shaft keratin expression and inhibited spontaneous HF regression (catagen) ex vivo. Collectively, these data (a) identify Wnt signaling as a novel, non-immune-inhibitory CsA target; (b) introduce SFRP1 as a physiologically important regulator of canonical β-catenin activity in a human (mini-)organ; and (c) demonstrate WAY-316606 to be a promising new promoter of human hair growth. Since inhibiting SFRP1 only facilitates Wnt signaling through ligands that are already present, this “ligand-limited” therapeutic strategy for promoting human hair growth may circumvent potential oncological risks associated with chronic Wnt over-activation. We used microarrays to identify novel hair growth promoting targets in human hair follicles through the use of cyclosporine A.

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FGF18 Signaling for Hair Cycle Resting Phase Determines Radioresistance of Hair Follicles by the Arrest of Hair Cycling

Project description:Telogen (resting phase) hair follicles are more radioresistant than anagen (growth phase) ones. Irradiation of BALB/c mice in the anagen phase with γ-rays at 6 Gy induced hair follicle dystrophy, whereas irradiation in the telogen phase induced the arrest of hair follicle elongation without any dystrophy after post-irradiation depilation. In contrast, FGF18 was highly expressed in the telogen hair follicles to maintain the telogen phase and also the quiescence of hair follicle stem cells. Therefore, the inhibition of FGF receptor signaling at telogen induced the dystrophy after post-irradiation depilation. In addition, the administration of recombinant FGF18 suppressed cell proliferation in the hair follicles and enhanced the repair of radiation-induced DNA damage, so FGF18 protected the anagen hair follicles against radiation damage to enhance hair regeneration. Moreover, FGF18 reduced the expression of cyclin B1 and cdc2 in the skin and FGF18 signaling induced G2/M arrest in the keratinocyte cell line HaCaT, although no obvious change of the expression of DNA repair genes was detected by DNA microarray analysis. These findings suggest that FGF18 signaling for the hair cycle resting phase causes radioresistance in telogen hair follicles by arresting the proliferation of hair follicle cells.

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Gene Expression in Unstaged Head Hair Follicles Plucked from Men and Women

Project description:Investigation of Gene Expression Profiling in Unstaged Head Hair Follicles Plucked from Men and Women Keywords: Gene Expression Profiling of Normal Hair Follicles

2006-06-30 | GSE3058 | GEO

Mutational burden in human hair follicles

Project description:We would like to dissect human hair follicles and assess the mutations found in diffferent parts of the follicle eg bulge, root etc. We can also compare this with mutations found in the surrounding epidermis of the same patients (this is done under a different study). This may provide insights into the origin of PTCH1 mutants frequently seen in basal cell carcinoma but so far not located in our whole epidermis work as well as defining the clonality of the hair follicle

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