Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis
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ABSTRACT:
SUBMITTER: Liu L
PROVIDER: S-EPMC10840369 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:Transcriptomic analysis of frontal fibrosing alopecia
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Project description:We undertook transcriptome profiling with RNA-sequencing of scalp skin from seven cases of European ancestry and seven matched controls.
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2017-09-04 | GSE101620 | GEO
Project description:Adipose-derived stem cells (ASCs) have shown efficacy in promoting hair growth, while DKK1 inhibits the WNT pathway, which is associated with hair loss. Our study focused on investigating the expression of DKK1 in alopecia areata (AA), a condition characterised by significant increases in the DKK1 levels in human and mouse ASCs. Treatment of interferon-γ increased the expression of DKK1 via STAT3 phosphorylation in ASCs. Treatment with recombinant DKK1 resulted in a decrease of cell growth in outer root sheath cells, whereas the use of a DKK1 neutralising antibody promoted hair growth. These results indicate that ASCs secrete DKK1, playing a crucial role in the progression and development of AA. Consequently, we generated DKK1 knockout (KO) ASCs using the Crispr/Cas9 system and evaluated their hair growth-promoting effects in an AA model. The DKK1 KO in ASCs led to enhanced cell motility and reduced cellular senescence by activating the WNT signalling pathway, while it reduced the expression of inflammatory cytokines by inactivating the NF-kB pathway. As expected, the intravenous injection of DKK1-KO-ASCs in AA mice, and the treatment with a conditioned medium derived from DKK1-KO-ASCs in hair organ culture proved to be more effective compared with the use of naïve ASCs and their conditioned medium. Overall, these findings suggest that DKK1 represents a novel therapeutic target for treating AA, and cell therapy using DKK1-KO-ASCs demonstrates greater efficiency.
| S-EPMC10905327 | biostudies-literature
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.
2017-09-04 | GSE101619 | GEO
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.
2017-09-04 | GSE101618 | GEO
Project description:BackgroundA recent study reported that papillary thyroid carcinoma (PTC) was associated with increased adrenergic nerve density. Meanwhile, emerging evidence suggested that tumor-innervating nerves might play a role in shaping the tumor microenvironment. We aimed to explore the potential interaction between neuronal markers and tumor microenvironmental signatures through a transcriptomic approach.MethodsmRNA sequencing was conducted using five pairs of PTC and adjacent normal tissues. The Gene Set Variation Analysis (GSVA) was performed to calculate enrichment scores of gene sets related to tumor-infiltrating immune cells and the tumor microenvironment. The potential interaction was tested using the expression levels of a series of neuronal markers and gene set enrichment scores.ResultsPTC tissues were associated with increased enrichment scores of CD8 T cells, cancer-associated fibroblasts, mast cells, and checkpoint molecules. The neuronal marker for cholinergic neurons was positively correlated with CD8 T cell activation, while markers for serotonergic and dopaminergic neurons showed an inverse correlation.ConclusionDistinct neuronal markers exerted different correlations with tumor microenvironmental signatures. Tumor-innervating nerves might play a role in the formation of the PTC microenvironment.
| S-EPMC9844349 | biostudies-literature
Project description:The pathogenesis of rheumatoid arthritis (RA) remains elusive. The initiation of joint degeneration is characterized by the loss of self-tolerance in peripheral joints. Ferroptosis, a form of regulated cell death, holds significant importance in the pathophysiology of inflammatory arthritis, primarily due to iron accumulation and the subsequent lipid peroxidation. The present study investigated the association between synovial lesions and ferroptosis-related genes using previously published data from rheumatoid patients. Transcriptome differential gene analysis was employed to identify ferroptosis-related differentially expressed genes (FRDEGs). To validate FRDEGs and screen hub genes, we used weighted gene co-expression network analysis (WGCNA) and receiver operating characteristic (ROC) curves. Subsequently, immune infiltration analysis and single cell analysis were conducted to investigate the relationship between various synovial tissues cells and FRDEGs. The findings were further confirmed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemical staining, and immunofluorescence techniques. Upon intersecting DEGs with ferroptosis-related genes, we identified a total of 104 FRDEGs. Through the construction of a protein-protein interaction (PPI) network, we pinpointed the top 20 most highly concentrated genes as hub genes. Subsequent analyses using ROC curve and WGCNA validated eight FRDEGs: TIMP1, JUN, EGFR, SREBF1, ADIPOQ, SCD, AR, and FABP4. Immuno-infiltration analyses revealed significant infiltration of immune cell in RA synovial tissues and their correlations with the FRDEGs. Notably, TIMP1 demonstrated a positive correlation with various immune cell populations. Single-cell sequencing date of RA synovial tissue revealed predominant expression of TIMP1 is in fibroblasts. RT-qPCR, immunohistochemistry, and immunofluorescence analyses confirmed significant upregulation of TIMP1 at both mRNA and protein levels in RA synovial tissues and fibroblast-like synoviocytes (FLS). The findings provide novel insights into pathophysiology of peripheral immune tolerance deficiency in RA. The dysregulation of TIMP1, a gene associated with ferroptosis, was significantly observed in RA patients, suggesting its potential as a promising biomarker and therapeutic target.
| S-EPMC11292532 | biostudies-literature
Project description:We have previously demonstrated that receptor-interacting serine threonine kinase 1 (RIPK1) is expressed in hair follicles and regulates the hair cycle. In a mouse model, RIPK1 inhibitors also accelerated the telogen-to-anagen transition and elongated the anagen period. Here, we first investigated the involvement of RIPK1 in alopecia areata (AA). The mRNA and protein expression of RIPK1 was increased in the skin of an AA mouse model. Single-cell RNA sequencing and immunohistochemistry showed that RIPK1 was highly increased in dendritic cells (DCs) and CD8+ T cells. RIPK1 inhibitors (i.e., Necrostatin-1s and GSK2982772) delayed the onset of AA in the mouse model and reduced the numbers of DCs and CD8+ T cells in AA skin. The RIPK1 inhibitors also increased the hair length in a mouse hair organ culture mimicking AA. Collectively, these results suggest that RIPK1 is involved in AA onset via modulating immune cells, and RIPK1 inhibitors could prevent AA onset.
| S-EPMC11855397 | biostudies-literature