ABSTRACT: Tissue and circulating microRNA co-expression analysis reveals potential involvement of miRNAs in the pathobiology of frontal fibrosing alopecia [skin]
Project description:Tissue and circulating microRNA co-expression analysis reveals potential involvement of miRNAs in the pathobiology of frontal fibrosing alopecia
Project description:Tissue and circulating microRNA co-expression analysis reveals potential involvement of miRNAs in the pathobiology of frontal fibrosing alopecia [blood]
Project description:Frontal fibrosing alopecia (FFA), a clinical variant of follicular lichen planus, is a predominantly postmenopausal, immune-mediated, inflammatory, primary lymphocytic cicatricial alopecia. FFA mainly involves the scalp, facial hair and eyebrows but also affects other body regions. MicroRNAs (miRNAs) have emerged as potential candidates of pathobiologic, diagnostic and therapeutic interest in chronic inflammatory, fibrotic and autoimmune diseases. To explore miRNAs in FFA for their disease relevance we isolated plasma from venous blood from 10 biopsy-proven treatment-naïve FFA cases and 10 matched controls and undertook miRNA expression analysis using the Human Fibrosis miRNA PCR Array (Qiagen). A separate cohort of 7 active FFA cases and 7 matched healthy controls were ascertained for tissue microRNA analysis and all 14 scalp-biopsy-extracted microRNA samples were subjected to microarray analysis on Affymetrix GeneChip miRNA 4.0 arrays. We generated a list of communities for the two skin tissue networks (cases and controls) and identified cluster centres (exemplars) as representative miRNAs of each community. Twenty exemplars in the control network were significantly enriched in the plasma (control) dataset compared to 27 for FFA. Amongst these, there were 17 miRNAs common in both networks, 9 of which were representative in the FFA disease phenotype. Random Forest analysis suggested that 4 circulating miRNAs (hsa-let-7d-5p, hsa-miR-18a-5p, has-miR-20a-5p and hsa-miR-19a-3p) can discriminate between FFA and controls. Our study of skin and plasma miRNA co-expression highlights circulating miRNAs of potential predictive value as biomarkers that should now be validated in larger cohorts.
Project description:Frontal fibrosing alopecia (FFA), a clinical variant of follicular lichen planus, is a predominantly postmenopausal, immune-mediated, inflammatory, primary lymphocytic cicatricial alopecia. FFA mainly involves the scalp, facial hair and eyebrows but also affects other body regions. MicroRNAs (miRNAs) have emerged as potential candidates of pathobiologic, diagnostic and therapeutic interest in chronic inflammatory, fibrotic and autoimmune diseases. To explore miRNAs in FFA for their disease relevance we isolated plasma from venous blood from 10 biopsy-proven treatment-naïve FFA cases and 10 matched controls and undertook miRNA expression analysis using the Human Fibrosis miRNA PCR Array (Qiagen). A separate cohort of 7 active FFA cases and 7 matched healthy controls were ascertained for tissue microRNA analysis and all 14 scalp-biopsy-extracted microRNA samples were subjected to microarray analysis on Affymetrix GeneChip miRNA 4.0 arrays. We generated a list of communities for the two skin tissue networks (cases and controls) and identified cluster centres (exemplars) as representative miRNAs of each community. Twenty exemplars in the control network were significantly enriched in the plasma (control) dataset compared to 27 for FFA. Amongst these, there were 17 miRNAs common in both networks, 9 of which were representative in the FFA disease phenotype. Random Forest analysis suggested that 4 circulating miRNAs (hsa-let-7d-5p, hsa-miR-18a-5p, has-miR-20a-5p and hsa-miR-19a-3p) can discriminate between FFA and controls. Our study of skin and plasma miRNA co-expression highlights circulating miRNAs of potential predictive value as biomarkers that should now be validated in larger cohorts.
Project description:Protein profiling offers an effective approach to characterizing the departure from normal of epidermis in disease states. The present investigation tested the hypothesis that the differentiation of epidermal corneocytes is perturbed in the forehead of subjects exhibiting frontal fibrosing alopecia. To this end, samples were collected by tape stripping from subjects diagnosed with this condition and compared to those from asymptomatic control subjects and from those exhibiting androgenetic alopecia. Unlike the latter, which exhibited only 3 proteins significantly different from controls, forehead samples from frontal fibrosing alopecia subjects displayed 72 proteins significantly different from controls, nearly two-thirds having lower expression. Comparison to corresponding profiles in scalp samples from frontal fibrosing alopecia and androgenetic alopecia suggested the perturbation of epidermal differentiation in the former was even greater in the scalp.
Project description:Summary statistics of a GWAS meta-analysis for frontal fibrosing alopecia (FFA). A total of 7,039,930 genotyped and imputed variants were used for 1,044 European severe FFA cases and 4,145 matched population controls.
Project description:Androgenetic alopecia (AGA) is characterized by a progressive and androgen-dependent loss of hair from the frontal and vertex regions of the scalp. Although large-scale genetic analyses have identified >300 genetic risk factors, the underlying causal genes and pathways, and their involvement in core pathophysiological mechanisms, remain unclear. In the present study, systematic profiling of differential mRNA and microRNA expression was performed in human hair follicle samples from frontal and occipital scalp regions. Taken together, the present data improve understanding of the genomic regions, genes, and pathways that are implicated in AGA pathobiology.
Project description:The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, except for the occipital region. To identify biological differences among HF subpopulations. Paired vertex and occipital HFs from 10 male AGA donors were collected for RNA-seq assay. Furthermore, hair follicle and cell experiments were conducted on the identified key genes to reveal their roles in AGA. Our study aimed to uncover potential lncRNA indicators for AGA and reveal the potential mechanism underlying the involvement of AL136131.3 in hair growth in AGA.
Project description:Two patients with alopecia areata were treated with systemic ruxolitinib. Skin biopsies were taken before starting treatment and 12 weeks after starting treatment. We used microarrays to assess changes in gene expression of affected skin before and after starting treatment Two patients with alopecia areata were recruited for our study. Skin biopsies of affected scalp were taken prior to starting treatment with oral ruxolinitib. Additional skin biopsies were taken 12 weeks after starting treatment. Scalp skin biopsies were taken from patients without alopecia areata for comparison. RNA was extracted, cDNA libraries were made and profiled on affymetrix microarray chips.