Comprehensive expression profiles of mRNAs, lncRNAs and miRNAs in Kashin-Beck disease identified by RNA-sequencing

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

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COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation

Viruses ◽

10.3390/v13061018 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1018

Author(s):

Abby C. Lee ◽

Grant Castaneda ◽

Wei Tse Li ◽

Chengyu Chen ◽

Neil Shende ◽

...

Keyword(s):

Rna Sequencing ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Expression Profiles ◽

Immune Dysregulation ◽

Left Ventricular ◽

Recurrent Event ◽

Healthy Controls ◽

Sequencing Data ◽

Peripheral Blood Mononuclear

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.

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Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis

BMC Medical Genomics ◽

10.1186/s12920-021-00989-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jin-Yu Sun ◽

Yang Hua ◽

Hui Shen ◽

Qiang Qu ◽

Jun-Yan Kan ◽

...

Keyword(s):

Extracellular Matrix ◽

Network Analysis ◽

Aortic Valve ◽

Aortic Valve Disease ◽

Expression Profiles ◽

Enrichment Analysis ◽

Valve Disease ◽

Hub Genes ◽

Calcific Aortic Valve Disease ◽

Underlying Mechanisms

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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Connective Tissue Metabolism and Gingival Overgrowth

Critical Reviews in Oral Biology & Medicine ◽

10.1177/154411130401500305 ◽

2004 ◽

Vol 15 (3) ◽

pp. 165-175 ◽

Cited By ~ 91

Author(s):

P. C. Trackman ◽

A. Kantarci

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Oral Hygiene ◽

Tissue Specificity ◽

Gingival Fibroblast ◽

Drug Induced ◽

Gingival Overgrowth ◽

Connective Tissue Metabolism ◽

Matrix Metabolism ◽

Systemic Health

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.

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Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease

Arthritis & Rheumatism ◽

10.1002/art.27282 ◽

2010 ◽

Vol 62 (3) ◽

pp. 771-780 ◽

Cited By ~ 74

Author(s):

Chen Duan ◽

Xiong Guo ◽

Xiao-Dong Zhang ◽

Han-Jie Yu ◽

Hua Yan ◽

...

Keyword(s):

Gene Expression ◽

Comparative Analysis ◽

Knee Osteoarthritis ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Northwestern China ◽

Beck Disease

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Signaling Mechanisms in the Regulation of Renal Matrix Metabolism in Diabetes

Experimental Diabetes Research ◽

10.1155/2012/749812 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 23

Author(s):

Meenalakshmi M. Mariappan

Keyword(s):

Extracellular Matrix ◽

Signaling Pathways ◽

Matrix Protein ◽

Structural Changes ◽

Mammalian Target Of Rapamycin ◽

Adverse Outcomes ◽

Matrix Proteins ◽

Extracellular Matrix Protein ◽

Renal Hypertrophy ◽

Matrix Metabolism

Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-)regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes.

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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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