Similar Datasets
Project description:EMT-related lncRNA expression profiles in keloid
| PRJNA755292 | ENA
Project description:Purpose: We aimed to identify the molecular drivers that initiate or sustain keloid pathogenesis. Method: Bulk tissue RNA sequencing of Asian keloid and normal tissues was performed to identify genes that contribute to keloid pathogenesis. We also established a preclinical model of inflammatory skin fibrosis by injecting C57BL/6 mice with bleomycin intradermally for 3 weeks to provide an alternative animal model of keloid scar. Result: Gene set enrichment analysis revealed upregulation of WNT5A gene expression, along with significant enrichment of genes related to EMT in keloid tissues. These results correlate with those of histological analysis in which human keloid tissues and the bleomycin-induced fibrosis animal model showed increased WNT5A expression along with EMT markers. Our in vitro data showed increased expression of the IL-6/JAK/STAT pathway and subsequent elevation in EMT markers on keratinocytes when co-cultured with WNT5A-activated fibroblasts or keloid fibroblasts. Silencing of WNT5A reversed the hyperactivation of the STAT pathway and EMT. Conclusion: IL-6 secreted from WNT5A-activated fibroblasts or keloid fibroblasts may induce adjacent keratinocytes to express EMT markers by activating the JAK/STAT signalling pathway. A better understanding of keloid pathogenesis and the role of WNT5A in EMT will promote the development of next-generation targeted treatments for keloid scars.
2021-05-06 | GSE173900 | GEO
Project description:Transcriptional profiling of active keloid lesion and adjacent control normal skin tissue from human. Each control and lesion sample was derived from a matched individual.
2017-07-01 | GSE90051 | GEO
Project description:Keloids are wounding-induced fibroproliferative human tumor–like skin scars of complex genetic makeup and poorly defined pathogenesis. Fibroblasts are the principal mediator of fibroproliferative disorders. To reveal dynamic epigenetic and transcriptome changes of keloid fibroblasts, a vertical study from RNA-seq and ATAC-seq analyses followed by in vivo confirmation of candidate molecule expression and subsequent functional testing was carried out using an early passage, freshly isolated keloid fibroblast cell strain and its paired normal control. These keloid fibroblasts produce keloid-like scars in a plasma clot-based skin equivalent humanized keloid animal model. RNA-seq analysis reveals that Hepatic fibrosis is the most significant pathway followed by Wnt–b-catenin signaling, TGF-b signaling, regulation of the EMT pathway, the STAT3 pathway, and adherens junction signaling. ATAC-seq analysis shows that STAT3 signaling is the most active pathway in keloid fibroblasts, followed by Wnt signaling (Wnt5) and regulation of the EMT pathway. Immunohistochemistry confirms that activated STAT3, (Tyr705 phospho-STAT3) and/or b-catenin are upregulated in dermal fibroblasts of keloid clinical specimens and mature keloid skin equivalent implants from the humanized mouse model compared to the normal control. The effect of STAT3 signaling on keloid fibroblast collagen expression was further tested in plasma clot-based skin equivalents using Cucurbitacin I, a selective JAK2/STAT3 inhibitor. A non-linear dose response of Cucurbitacin I was observed in collagen type I expression indicating a likely role of STAT3 signaling pathway in keloid pathogenesis. This work also demonstrates the utility of the recently established humanized keloid mouse model in exploring the mechanism of keloid formation.
2020-01-11 | GSE125022 | GEO
Project description:Keloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes. Skin and scar tissues were obtained for isolation of primary keratinocytes and fibroblasts. Keloid scars were excised from patients undergoing scar excision surgery, normal skin samples were isolated from patients undergoing elective plastic surgery. Primary culters were prepared for keratinocytes and fibroblasts, and were harvested for analysis up to passage three. Nine keloid scars, for adjacent non-lesional keloid skin samples, and three normal skin samples were obtained and cultured. RNA was isolated using RNeasy, and quality verified using an Agilent 2100 Bioanalyzer. Labeling and hybridization to Affymetrix Human Gene 1.0 ST microarray chips was performed by the Vanderbilt Genome Sciences Resource at Vanderbilt University Medical Center.
2013-05-28 | E-GEOD-44270 | biostudies-arrayexpress
Project description:Microarray analysis was used to determine the expression profiles of lncRNAs and mRNAs between 3 pairs of earlobe keloid and normal specimens. Results provide insight into involement of lncRNAs in the pathological process of earlobe keloid formation. 3 pairs of earlobe keloid and normal specimens.
2016-06-14 | E-GEOD-83286 | biostudies-arrayexpress
Project description:In this study, we aimed to elucidate the profile of lesional and non-lesional keloid skin compared to normal skin. We performed gene (RNAseq, qRT-PCR) and protein (immunohistochemistry) expression analyses on biopsy specimens obtained from lesional and non-lesional skin of African American (AA) keloid patients compared to healthy skin from AA controls. We found that lesional versus normal skin showed significant up-regulation of markers of T-cell activation/migration (ICOS, CCR7), Th2- (IL-4R, CCL11, TNFSF4/OX40L), Th1- (CXCL9/CXCL10/CXCL11), Th17/Th22- (CCL20, S100As) pathways, and JAK/STAT-signaling (JAK3) (false-discovery rate [FDR]<0.05).
2020-10-19 | GSE158395 | GEO
Project description:Keloid scars is a pathologic fibro-proliferative disorders of the skin, which exhibit abnormal phenotypes including fibroblasts proliferation and collagen deposits. There have been several treatments of keloids including conventional surgical therapies and adjuvant therapies, but a high recurrence rate of keloids was also observed after treatment. Quantitative proteomics approach has been proved an efficient approach to investigate pathological mechanism and novel biomarkers. In this study, we present a label-free quantitative proteomics analysis to explore differential protein expression profiles in normal skin and keloid scar tissues based on nano-liquid chromatography and tandem mass spectrometry (Nano-LC–MS/MS). The study results displayed a more comprehensive keloid protein expression landscape and provided novel pathological insight of keloid.
2023-03-11 | PXD029631 | Pride
Project description:Skin specimens were derived from involved skin of 3 systemic scleroderma (SSc), 3 localized scleroderma (LSc) and 3 keloid patients. These skin samples and 3 control skins were collected and fixed in formaldehyde immediately after resections. The microRNA (miRNA) isolation from human skin tissue was performed using miRNeasy FFPE kit (Qiagen). For PCR array, miRNAs were reverse-transcribed into first strand cDNA using RT2 miRNA First Strand Kit (SABiosciences). A mixture of equal amounts of miRNAs from 3 normal skins, 3 SSc, 3 LSc or 3 keloid were prepared, and miRNA expression profile in each disease in vivo was evaluated using RT2 Profiler PCR Array. The cDNA was mixed with RT2 SYBR Green/ROX qPCR Master Mix and the mixture was added into 96-well RT2 miRNA PCR Array that includes primer pairs for 88 human miRNAs (SABiosciences). Skin specimens were derived from involved skin of 3 systemic scleroderma (SSc), 3 localized scleroderma (LSc) and 3 keloid patients. These skin samples and 3 control skins were collected and fixed in formaldehyde immediately after resections. Control donors were each matched with diseases for age, sex, and biopsy site.
2013-01-15 | E-GEOD-43469 | biostudies-arrayexpress
Project description:Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.
2023-07-31 | PXD037401 | Pride