Cicatricial Alopecia pathogenesis: Uniqueness or similarities between lymphocytic subtypes Lichen planopilaris (LPP) and Central centrifugal cicatricial alopecia (CCCA)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE59131 | GEO | 2021/12/21
REPOSITORIES: GEO
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Project description:Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. Laser capture microdissection of bulge cells from biopsies of lesional and non-lesional scalp skin from adult LPP patients were analyzed by microarray analysis.
2013-07-04 | E-MEXP-3859 | biostudies-arrayexpress
Project description:Lichen planopilaris (LPP) and pseudopelade of Brocq (PPB) are two scarring alopecia diagnoses that often exhibit similar clinical features. Some suggest LPP and PPB are not distinct diseases, but rather different clinical presentations in a spectrum derived from the same underlying pathogenetic mechanism. We explored the degree of similarity between LPP and PPB gene expression patterns and the potential for common and unique gene pathway and gene activity in LPP and PPB using microarrays. Microarray analysis, using a 21K cDNA set was performed on pairs of biopsies obtained from affected and unaffected scalp of untreated patients (4 LPP and 4 PPB biopsy pairs). Diagnosis was confirmed by histopathology. Significantly differentially expressed genes were identified by analysis of microarray results in various data sets and screened for signaling pathway involvement. Selected genes were validated by quantitative PCR and immunohistology. The global gene expression profiles in LPP and PPB versus comparative intra-control scalp tissue were distinguishable by Significance Analysis of Microarrays (SAM). Specific genes, such as MMP11, were identified with significantly differential expression in association with LPP versus PPB. There was very limited commonality in the gene expression profiles between LPP and PPB. Our findings may have important implications for understanding the pathogenesis of LPP and PPB at the molecular level. Results suggest LPP and PPB involve different mechanisms of disease development and can be regarded as biologically distinct cicatricial alopecia diagnoses. Genes that we have identified may potentially be useful as markers of the respective diagnoses.
2008-07-01 | GSE11905 | GEO
Project description:Mitochondrial dysfunction is implicated in myriad diseases. However, there is no single platform that facilitates mapping of mitochondrial pathways and processes essential for health and those that are defective in disease. Here, we manually curated 1008 mitochondrial proteins to create a database of 31 mitochondrial pathways and processes and named the database as ‘MitoGyan’. ‘Gyan’ in Sanskrit means knowledge. We also developed a mitochondria associated metabolic pathways visualization tool called MitoCyc within HumanCyc. Using these novel resources and an integrated ‘Omics’ approach, we demonstrate that mitochondrial dysfunction occurs early in a rare, inflammatory hair disease called Frontal Fibrosing Alopecia (FFA). Transmission electron microscopy and mass spectrometry show morphological and functional changes in the mitochondria of FFA hair follicles. Our data suggests that mitochondrial dysfunction induces oxidative stress and an impairment of the ubiquitin proteasome system (UPS) in FFA. We propose that mitochondria-targeted antioxidants provide a new therapeutic strategy for FFA. Microarray analyses of FFA was undertaken to decipher pathophysiological pathways of FFA leading to disease intitiation and progression
2021-12-21 | GSE58934 | GEO
Project description:Alopecia areata (AA) is an autoimmune disease that attacks anagen hair follicles. Gene array in graft-induced C3H/HeJ mice revealed that genes involved in retinoic acid (RA) synthesis were increased, whereas RA degradation genes were decreased in AA compared with sham controls. This was confirmed by immunohistochemistry in biopsies from patients with AA and both mouse and rat AA models. RA levels were also increased in C3H/HeJ mice with AA. C3H/HeJ mice were fed a purified diet containing one of the four levels of dietary vitamin A or an unpurified diet 2 weeks before grafting and disease progression followed. High vitamin A accelerated AA, whereas mice that were not fed vitamin A had more severe disease by the end of the study. More hair follicles were in anagen in mice fed high vitamin A. Both the number and localization of granzyme B-positive cells were altered by vitamin A. IFN? was also the lowest and IL13 highest in mice fed high vitamin A. Other cytokines were reduced and chemokines increased as the disease progressed, but no additional effects of vitamin A were seen. Combined, these results suggest that vitamin A regulates both the hair cycle and immune response to alter the progression of AA.
| S-EPMC3546144 | biostudies-literature
Project description:BackgroundAlopecia areata (AA) describes a sudden localized patchy alopecia. The cause of AA is not completely clear and its incidence may be related to genetic, autoimmune, and environmental factors.AimTo explore the possible mechanisms of AA and to provide a basis for the early diagnosis and treatment of AA.MethodsGene microarray data from 122 scalp skin biopsy tissue samples from patients with AA or healthy controls from the Gene-Cloud of Biotechnology Information database were analyzed using bioinformatics analysis methods. Molecular network analysis of the differentially expressed genes (DEGs) was conducted by Cytocluster using the Molecular Complex Detection (MCODE) algorithm.ResultsThe gene expression profile of skin lesions from patients with AA was significantly altered, with 111 DEGs found in the skin lesions of AA, compared with that of the healthy skin. The DEGs were mainly related to biological processes such as the development of the epidermis and inflammatory reaction. The protein-protein interaction network analysis of DEGs revealed bone morphogenetic protein 2 (BMP2) as a core protein interaction network. BMP2 acted not only via the inflammatory response but also via the signaling pathways in epithelial cell development and epidermal cell differentiation to affect the epidermal development. MCODE analysis further showed that keratins (KRTs) and keratin-associated proteins (KRTAPs) can affect the epidermal development via the epidermal development pathway.ConclusionsThe abnormal development of the epidermis and inflammatory reactions in skin tissue play important roles in the pathogenesis of AA and are closely related to BMP2, KRTs, and KRTAPs genes.LimitationsOur study was limited by experimental verification.
| S-EPMC6340232 | biostudies-literature
Project description:Alopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression analysis of 96 human scalp skin biopsy specimens from AA or normal control subjects. Based on gene expression profiling, samples formed distinct clusters based on the presence or absence of disease as well as disease phenotype (patchy disease compared with alopecia totalis or universalis). Differential gene expression analysis allowed us to robustly demonstrate graded immune activity in samples of increasing phenotypic severity and generate a quantitative gene expression scoring system that classified samples based on interferon and cytotoxic T lymphocyte immune signatures critical for disease pathogenesis.
| S-EPMC4909368 | biostudies-literature
Project description:The natural history of central centrifugal cicatricial alopecia (CCCA) is widely variable. Some patients experience rapid progression to extensive, end-stage disease while others never approach extensive involvement over decades, suggesting heterogeneity in CCCA disease phenotype. To better characterize clinically severe disease in CCCA, tissue samples were obtained from the peripheral, hair-bearing lesional scalp of women with clinically focal, limited and extensive CCCA disease involvement. A microarray analysis was conducted to identify differential expression of genes previously identified to be preferentially expressed in the lesional scalp vs. non-lesional scalp of CCCA patients. Clinically extensive, severe CCCA was characterized by increased expression of MMP9, SFRP4 and MSR1 when directly compared with focal and limited disease. These biomarkers correspond to dysregulated pathways of fibrosis, Wnt signalling and macrophage-mediated inflammatory processes respectively. These findings hold significance for both possible targets for future study of prognostic markers of disease severity and new potential therapeutic targets. In summary, this study suggests clinically extensive, severe CCCA may have a differential gene expression pattern in the lesional scalp of affected patients, in addition to its clinical distinction.
| S-EPMC9127746 | biostudies-literature
Project description:Braun/murein lipoprotein (Lpp) is one of the major outer membrane components of gram-negative bacteria belonging to the enterobacteriaceae family that that is involved in inflammatory responses and septic shock. We previously characterized a delta-lpp isogenic mutant of Yersinia pestis CO92 and found that this mutant was defective in surviving in macrophages and was attenuated in a mouse inhalation model of plague when compared to the highly virulent wild-type (WT) bacterium. To better understand how deletion of the lpp gene might affect Yersinia virulence, we performed global transcriptional profiling of the genes in the WT Y. pestis CO92 and its delta-lpp mutant by using microarrays. The organisms were cultured at both 26 and 37 degrees Celsius to simulate the flea vector and mammalian host environments, respectively. Our data revealed vastly different effects of lpp mutation on the transcriptomes of Y. pestis grown at 37 versus 26°C. While the absence of Lpp resulted mainly in the down-regulation of metabolic genes at 26°C, the Y. pestis CO92 lpp mutant cultured at 37°C exhibited profound alterations in stress response and virulence genes, compared to the WT bacterium. We further investigated one of the stress-related genes (htrA) down-regulated in the lpp mutant relative to WT Y. pestis, as HtrA was previously shown to be important for intracellular survival of Y. enterocolitica in macrophages. Indeed, complementation of the delta-lpp mutant with the htrA gene in trans restored intracellular survival of the Y. pestis lpp mutant. Our results support a role for Lpp in Y. pestis CO92 adapatation to the host environment, possibly via transcriptional activation of htrA.
2010-06-04 | GSE19840 | GEO
Project description:This study was undertaken to compare efficacy of MJC13 and the classic AR antagonist flutamide. Both compounds modulate endogenous AR target gene expression in Prostate cancer cells in a similar fashion despite different mechanisms of action.
2015-12-31 | GSE65562 | GEO
Project description:Background: Central Centrifugal Cicatricial Alopecia (CCCA) is a primary cicatricial alopecia that most commonly affects women of African descent. Like CCCA, fibroproliferative disorders (FPDs) such as keloids, atherosclerosis and fibroids, are characterized by low-grade inflammation and irritation resulting in end stage fibrosis. Objective: We sought to determine if fibroproliferative genes were upregulated in patients with CCCA Methods: Five patients with biopsy proven CCCA were recruited for this study. Two scalp biopsies were obtained from each patient; one from CCCA affected vertex scalp and one from the unaffected occipital scalp. Microarray analysis was performed to determine the differential gene expression patterns Results: Several pathways responsible for excess collagen deposition and aberrant wound healing were up-regulated in CCCA affected scalp when compared to unaffected scalp with patterns similar to other FPDs. Genes downregulated in CCCA affected tissue included those with roles in lipid metabolism and fatty acid biosynthesis. Limitations: Small sample size and the use of whole skin tissue for analysis. Conclusion: We have identified the up-regulation of critical genes implicated in fibroproliferative disorders in the gene expression profile of patients with CCCA. These findings may help identify future therapeutic targets for this otherwise difficult to treat condition.
2021-03-22 | GSE113052 | GEO