Extracellular Matrix and Integrin Expression Profiles in Fuchs Endothelial Corneal Dystrophy Cells and Tissue Model

Abstract Background Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear. Methods The gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by ‘limma’ and ‘weighted gene co-expression network analysis (WGCNA)’ package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein–protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation. Results We identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively. Conclusions This study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.

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Global gene expression profiles reveal an increase in mRNA levels of collagens, MMPs, and TIMPs in late radiation enteritis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00088.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. G875-G885 ◽

Cited By ~ 46

Author(s):

Carine Strup-Perrot ◽

Denis Mathé ◽

Christine Linard ◽

Dominique Violot ◽

Fabien Milliat ◽

...

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Expression Profiles ◽

Cdna Array ◽

Muscularis Propria ◽

Gelatin Zymography ◽

Tissue Inhibitors Of Metalloproteinases ◽

Radiation Enteritis ◽

Mrna Levels ◽

Fixed Tissue

Radiation enteritis, a common complication of radiation therapy for abdominal and pelvic cancers, is characterized by severe transmural fibrosis associated with mesenchymal cell activation, tissue disorganization, and deposition of fibrillar collagen. To investigate the mechanisms involved in this pathological accumulation of extracellular matrix, we studied gene expression of matrix components along with that of genes involved in matrix remodeling, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). Hybrid selection on high-density cDNA array, real-time RT-PCR, gelatin zymography and imunohistochemistry were used to characterize the mRNA expression profile, activity, and tissue location of extracellular matrix-related genes in radiation enteritis compared with healthy ileum. cDNA array analysis revealed a strong induction of genes coding for collagens I, III, IV, VI, and VIII, SPARC, and tenascin-C, extracellular-matrix degrading enzymes (MMP-1, -2, -3, -14, -18+19), and metalloproteinase inhibitors (TIMP-1, -2, plasminogen activator inhibitor-1) in radiation enteritis. This increase was correlated with the degree of infiltration of the mucosa by inflammatory cells, and the presence of differentiated mesenchymal cells in the submucosa and muscularis propria. Despite the fact that expression of collagens, MMPs, and TIMPs simultaneously increase, quantification of net collagen deposition shows an overall accumulation of collagen. Our results indicate that late radiation enteritis tissues are subjected to active process of fibrogenesis as well as fibrolysis, with a balance toward fibrogenesis. This demonstrates that established fibrotic tissue is not scarred fixed tissue but is subjected to a dynamic remodeling process.

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Respiratory Syncytial Virus Infection Induces Chromatin Remodeling to Activate Growth Factor and Extracellular Matrix Secretion Pathways

Viruses ◽

10.3390/v12080804 ◽

2020 ◽

Vol 12 (8) ◽

pp. 804 ◽

Cited By ~ 1

Author(s):

Xiaofang Xu ◽

Dianhua Qiao ◽

Morgan Mann ◽

Roberto P. Garofalo ◽

Allan R. Brasier

Keyword(s):

Extracellular Matrix ◽

Respiratory Syncytial Virus ◽

Growth Factor ◽

Epithelial Cells ◽

Expression Profiles ◽

Open Chromatin ◽

High Confidence ◽

Chromatin Domains ◽

Rsv Infection ◽

Syncytial Virus

Lower respiratory tract infection (LRTI) with respiratory syncytial virus (RSV) is associated with reduced lung function through unclear mechanisms. In this study, we test the hypothesis that RSV infection induces genomic reprogramming of extracellular matrix remodeling pathways. For this purpose, we sought to identify transcriptionally active open chromatin domains using assay for transposase-accessible-next generation sequencing (ATAC-Seq) in highly differentiated lower airway epithelial cells. High confidence nucleosome-free regions were those predicted independently using two peak-calling algorithms. In uninfected cells, ~12,650 high-confidence open chromatin regions were identified. These mapped to ~8700 gene bodies, whose genes functionally controlled organelle synthesis and Th2 pathways (IL6, TSLP). These latter cytokines are preferentially secreted by RSV-infected bronchiolar cells and linked to mucous production, obstruction, and atopy. By contrast, in RSV infection, we identify ~1700 high confidence open chromatin domains formed in 1120 genes, primarily in introns. These induced chromatin modifications are associated with complex gene expression profiles controlling tyrosine kinase growth factor signaling and extracellular matrix (ECM) secretory pathways. Of these, RSV induces formation of nucleosome-free regions on TGFB1/JUNB//FN1/MMP9 genes and the rate limiting enzyme in the hexosamine biosynthetic pathway (HBP), Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2). RSV-induced open chromatin domains are highly enriched in AP1 binding motifs and overlap experimentally determined JUN peaks in GEO ChIP-Seq data sets. Our results provide a topographical map of chromatin accessibility and suggest a growth factor and AP1-dependent mechanism for upregulation of the HBP and ECM remodeling in lower epithelial cells that may be linked to long-term airway remodeling.

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Spatiotemporal Coupling of Focal Extracellular Matrix Degradation and Reconstruction in the Menstrual Human Endometrium

Endocrinology ◽

10.1210/en.2009-0750 ◽

2009 ◽

Vol 150 (11) ◽

pp. 5094-5105 ◽

Cited By ~ 42

Author(s):

Héloïse P. Gaide Chevronnay ◽

Christine Galant ◽

Pascale Lemoine ◽

Pierre J. Courtoy ◽

Etienne Marbaix ◽

...

Keyword(s):

Extracellular Matrix ◽

Expression Profiles ◽

Xenograft Model ◽

Gene Expression Profiles ◽

Functional Layer ◽

Processing Enzymes ◽

Mouse Xenograft Model ◽

Glandular Cells ◽

Tissue Degradation ◽

Ecm Degradation

Coupling of focal degradation and renewal of the functional layer of menstrual endometrium is a key event of the female reproductive biology. The precise mechanisms by which the various endometrial cell populations control extracellular matrix (ECM) degradation in the functionalis while preserving the basalis and the respective contribution of basalis and functionalis in endometrium regeneration are still unclear. We therefore compared the transcriptome of stromal and glandular cells isolated by laser capture microdissection from the basalis as well as degraded and preserved areas of the functionalis in menstrual endometria. Data were validated by in situ hybridization. Expression profile of selected genes was further analyzed throughout the menstrual cycle, and their response to ovarian steroids withdrawal was studied in a mouse xenograft model. Immunohistochemistry confirmed the results at the protein level. Algorithms for sample clustering segregated biological samples according to cell type and tissue depth, indicating distinct gene expression profiles. Pairwise comparisons identified the greatest numbers of differentially expressed genes in the lysed functionalis when compared with the basalis. Strikingly, in addition to genes products associated with tissue degradation (matrix metalloproteinase and plasmin systems) and apoptosis, superficial lysed stroma was enriched in gene products associated with ECM biosynthesis (collagens and their processing enzymes). These results support the hypothesis that fragments of the functionalis participate in endometrial regeneration during late menstruation. Moreover, menstrual reflux of lysed fragments overexpressing ECM components and adhesion molecules could easily facilitate implantation of endometriotic lesions.

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