Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of ECM rigidity on normal and keloid dermal fibroblasts

ABSTRACT: This study investigated the effects of extracellular matrix (ECM) rigidty on gene expression patterns in normal dermal fibroblasts (NDFs) and keloid dermal fibroblasts (KDFs). Cells were cultured on collagen coated polyacrylamide hydrogels with elastic moduli mimicking normal skin (8 kPa) or keloid scar tissue (214 kPa), and changes in gene expression were profiled using next-generation RNA-sequencing. Differential gene expression analysis identified overall significant differences in gene expression between the NDF and KDF populations. Despite high levels of inter-patient heterogeneity in the KDF samples, further principal components analysis revealed a subset of genes (PC5) that were specifically regulated by ECM rigidity. Gene set enrichment analysis of the PC5 genes identified classic pathways associated with mechanotransduction, including Hippo Signalling and Regulation of the Actin Cytoskeleton, as well as genes associated with the Autophagy pathway. Additional in vitro studies and human tissue staining confirmed the biomechanical regulation of autophagic flux in NDFs and KDFs and differential remodelling of the lysosome in KDFs and keloid scars. Together, these findings implicate autophagy and lysosomal remodelling as biomechanically dysregulated pathways in keloid fibroblasts, and these mechanisms may contribute to scar pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246562 | GEO | 2023/11/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Keratinocyte and fibroblast gene expression in skin and keloid scar tissue

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

Effects of ECM rigidity on normal and keloid dermal fibroblasts

Project description:Effects of ECM rigidity on normal and keloid dermal fibroblasts

| PRJNA1033633 | ENA

A microarray of circular RNAs in human keloid dermal fibroblasts

Project description:To further explore the expression of circular RNAs in keloid，we have completed the Arraystar Human circRNA Array V2 analysis of the 8 samples，including 4 patients-derived keloid dermal fibroblasts and 4 normal dermal fibroblasts.

2022-02-23 | GSE184097 | GEO

The Matrisome Reveals the Characterization of Skin Keloid Microenvironment

Project description:Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified, and the pathological mechanism of keloid formation was characterized using large-scale, quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties, key pathways, and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed the involvement of estrogen signaling pathways in keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

2020-05-08 | PXD019052 |

Different characteristics of different scar fibroblasts

Project description:The goal of this study is to compare the different characteristics of fibroblasts from normal, hypertrophic and keloid scar through RNA-seq.

2022-08-06 | GSE210434 | GEO

Quantitative proteomic analysis of keloid scars and normal skin tissues

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

Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymalfibroblastsin human skin fibrotic diseases

Project description:Skin fibrotic disease representsa major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix.Fibroblasts are found to be heterogeneous in multiple fibrotic diseases,but the fibroblast heterogeneity of skin fibrotic diseases remains unknown.In this study, we performed single-cell RNA-seq in keloid, a paradigm of skin fibrotic diseases, andnormal scardermis tissues.Our results indicate that keloid and normal scar fibroblasts could be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory.The percentage of mesenchymal fibroblast subpopulationincreased significantly in keloid compared to normal scar. Interestingly, we also found increasing mesenchymal fibroblast subpopulation in scleroderma, another skin fibrotic disease.Function studies showed that the mesenchymal fibroblasts promoted collagen synthesis of the other fibroblasts in keloid partiallythrough secreting POSTN. These findings will help us understandskin fibroticpathogenesis in depth,and provided potential target cells for fibrotic diseases therapies.

2021-05-23 | GSE163973 | GEO

The Role of the Mammalian Target of Rapamycin in Keloid and Hypertrophic Scars

Project description:We hypothesize that, the mTOR pathway is a dominant pathway in cultured keloid and hypertrophy scar fibriblasts compared to normal skin cells. Certain pathway changes can be detected after medication treatment. Global gene expression in RNA samples from rapamycin and tacrolimus treated fibroblasts (from normal skin and hypertrophic scars, keloid scars) is assayed to study the possibility to use mTOR inhibitors as potential drug to treat abnormal scarring. We investigated the difference between normal wound healing and hypertrophic scars and keloids as well.

2014-05-20 | E-MTAB-2509 | biostudies-arrayexpress

Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human skin fibrotic diseases (RNA-seq)

Project description:Skin fibrotic disease representsa major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix.Fibroblasts are found to be heterogeneous in multiple fibrotic diseases,but the fibroblast heterogeneity of skin fibrotic diseases remains unknown.In this study, we performed single-cell RNA-seq in keloid, a paradigm of skin fibrotic diseases, andnormal scardermis tissues.Our results indicate thatkeloid and normal scar fibroblasts could be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory.The percentage of mesenchymal fibroblast subpopulationincreased significantly in keloid compared to normal scar. Interestingly, we also found increasing mesenchymal fibroblast subpopulation in scleroderma, another skin fibrotic disease.Function studies showed that the mesenchymal fibroblasts promoted collagen synthesis of the other fibroblasts in keloid partiallythrough secreting POSTN. These findings will help us understandskin fibroticpathogenesis in depth,and provided potential target cells for fibrotic diseases therapies.

2021-06-01 | GSE175866 | GEO

WNT5A Drives IL-6-Dependent Epithelial-to-Mesenchymal Transition via the JAK/STAT Pathway in Keloid Pathogenesis

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data