A novel miRNA-4484 is up-regulated on microarray and associated with increased MMP-21 expression in serum of systemic sclerosis patients
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PROVIDER: PRJNA565694 | ENA |
REPOSITORIES: ENA
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Project description:Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease, characterized by fibrosis and ECM deposition in skin and internal organs, autoimmunity, and changes in the microvasculature. Profiling of circulating miRNAs in serum has been found to be changed in pathological states, creating new possibilities for molecular diagnostics as blood-based biomarkers. This study was designed to identify miRNAs that are differentially expressed in SSc and might be potentially contributing to the disease etiopathogenesis or be used for diagnostic purposes. Thus, we compared the expression pattern of multiple miRNAs in serum of 10 SSc patients to 6 healthy controls using microarray analysis, and RT-qPCR to confirm the obtained results. In addition, bioinformatics analysis was performed to explore miRNAs target genes and the signaling pathways that may be potentially involved in SSc pathogenesis. Our study shows a different expression of 15 miRNAs in SSc patients. We identified that miR-4484, located on chromosome 10q26.2, was an 18-fold up-regulated in SSc patients compared to a control group. Bioinformatics analysis of the miR-4484 target genes and the signaling pathways showed that it might be potentially involved in the TGF-β signaling pathway, ECM-receptor interaction, and metalloproteinases expression. Based on the chromosomal location, the most interesting target gene of miR-4484 may be MMP-21. We found that the expression of MMP-21 significantly increased in SSc patients compared to healthy subjects (P<0.05). Our results suggest that miR-4484, and MMP-21 might be novel serum biomarkers that may correspond to pathological fibrosis in SSc, but it needs to be validated in further studies.
2019-10-15 | GSE137472 | GEO
Project description:Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease, characterized by fibrosis and ECM deposition in skin and internal organs, autoimmunity, and changes in the microvasculature. Profiling of circulating miRNAs in serum has been found to be changed in pathological states, creating new possibilities for molecular diagnostics as blood-based biomarkers. This study was designed to identify miRNAs that are differentially expressed in SSc and might be potentially contributing to the disease etiopathogenesis or be used for diagnostic purposes. Thus, we compared the expression pattern of multiple miRNAs in serum of 10 SSc patients to 6 healthy controls using microarray analysis, and RT-qPCR to confirm the obtained results. In addition, bioinformatics analysis was performed to explore miRNAs target genes and the signaling pathways that may be potentially involved in SSc pathogenesis. Our study shows a different expression of 15 miRNAs in SSc patients. We identified that miR-4484, located on chromosome 10q26.2, was an 18-fold up-regulated in SSc patients compared to a control group. Bioinformatics analysis of the miR-4484 target genes and the signaling pathways showed that it might be potentially involved in the TGF-? signaling pathway, ECM-receptor interaction, and metalloproteinases expression. Based on the chromosomal location, the most interesting target gene of miR-4484 may be MMP-21. We found that the expression of MMP-21 significantly increased in SSc patients compared to healthy subjects (P?<?0.05). Our results suggest that miR-4484, and MMP-21 might be novel serum biomarkers that may correspond to pathological fibrosis in SSc, but it needs to be validated in further studies.
| S-EPMC6776520 | biostudies-literature
Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage, and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lung of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. Here we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1, DNAM-1), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Further, CD226highCD8+ T cells from SSc patients produced abundant IL-13 and were positively correlated with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 impaired IL-13 production and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and are involved in SSc pathogenesis via the production of profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc. We first purified effector memory CD8+ T cells (CD3+CD8+CD45RO+CD62L+ cells) from peripheral blood by cell sorting and subsequently performed cDNA microarray analysis of the sort-purified effector memory CD8+ T cells from 9 SSc patients and 5 healthy controls.
2014-12-06 | E-GEOD-63903 | biostudies-arrayexpress
Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage, and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lung of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. Here we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1, DNAM-1), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Further, CD226highCD8+ T cells from SSc patients produced abundant IL-13 and were positively correlated with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 impaired IL-13 production and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and are involved in SSc pathogenesis via the production of profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc.
2014-12-06 | GSE63903 | GEO
Project description:BACKGROUND:Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs. The objectives were to investigate clinical correlations of serum calpain activity and high mobility group box 1 (HMGB1) levels with immunological and clinical traits. METHODS:A total of 31 patients with SSc, 20 age- and gender-matched healthy control subjects (HC), and 10 patients with other connective tissue diseases (CTD) were recruited in the study. We measured serum calpain activity and HMGB1 levels and analyzed the datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) from Gene Expression Omnibus (GEO) database to explore the potential mechanism by which calpain exerts its function through bioinformatics methods. RESULTS:Serum calpain activity was significantly increased in patients with SSc compared with those in HC and in patients with CTD and was correlated with serum HMGB1 levels, modified Rodnan skin score, erythrocyte sedimentation rate, mean platelet volume, and plateletcrit. Notably, serum calpain activity and HMGB1 levels in SSc patients with interstitial lung disease (ILD) were significantly higher than those in SSc patients without ILD. Serum calpain activity and HMGB1 levels could be the independent risk factors for SSc-ILD and novel biomarkers in patients with SSc. CONCLUSION:This is the first study that reports increased serum calpain activity and the correlation between calpain and HMGB1 in patients with SSc or SSc-ILD. The serum calpain activity and HMGB1 levels may serve as measures of ILD in patients with SSc. Also, calpain and HMGB1 could be potential therapeutic targets for patients with SSc or SSc-ILD in the future.
| S-EPMC7216546 | biostudies-literature
Project description:To investigate the miRNA signature in the serum of systemic sclerosis (SSc) patients. The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Patients fulfilling the ACR/EULAR 2013 classification criteria were classified in relation to the extent of skin fibrosis as limited cutaneous (lcSSc) or diffuse cutaneous SSc (dcSSc); patients fulfilling the classification criteria without skin fibrosis will be referred to as non-cutaneous SSc (ncSSc). MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease.The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR. MiR-483-5p expression was further analysed in the serum of patients with localized scleroderma (LoS) (n=22), systemic lupus erythematosus (SLE) (n=33) and primary Sjögren’s syndrome (pSS) (n=23). The function of miR-483-5p was examined by transfecting miR-483-5p into primary human dermal fibroblasts and pulmonary endothelial cells.30 miRNAs were significantly increased in patients with SSc. Of these, miR-483-5p showed reproducibly higher levels in an independent SSc cohort and was also elevated in patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not differentially expressed in patients with SLE or pSS, whereas it was up-regulated in LoS, indicating that this miRNA could be involved in the development of skin fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial cells modulated the expression of fibrosis-related genes.Our findings showed that miR-483-5p is up-regulated in the serum of SSc patients, from the early stages of the disease onwards, and indicated its potential function as a fine regulator of fibrosis in SSc.
2018-02-15 | GSE108918 | GEO
Project description:Matrix metalloprotease (MMP) -2 has been reported to be up-regulated in skeletal muscle in the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. However, the role of MMP-2 in dystrophin-deficient muscle is not well known. The aim of this study was to verify the role of MMP-2 in dystrophin-deficient muscle by using mdx mice with genetic ablation of MMP-2 (mdx/MMP-2-/-). Gene expression profiles were analyzed in the skeletal muscle of mdx and mdx/MMP-2-/- mice at 1 and 3 months of age.
2011-02-19 | GSE27129 | GEO
Project description:MT1-MMP and MT2-MMP double deficiency in mice leads to development of a placental defect resulting in embryonic death after E10.5. The protein substrate for these two proteases in placenta is unknown, which poses an obstacle in uncovering of molecular mechanism behind the observed placental defect. In search for a potential substrate for these two proteases in placenta we have employed whole genome microarray expression profiling as a discovery platform to identify genes, expression of which might be affected by double MMP deficiency. Fetal parts of mouse placentas were isolated from E10.5 placentas of different genotypes for MT1- and MT2-MMP.
2010-03-09 | E-GEOD-18604 | biostudies-arrayexpress
Project description:In order to investigate the impact of MMP-14 (MT1-MMP) on the transcriptomes of a human breast adenocarcinoma cell line, we performed a microarray analysis from RNAs isolated from MCF-7 cells expressing either an empty vector (VEC) or human MMP-14 cDNA (MT1) in monolayer growth conditions. MCF-7 cells were stably transfected with either an empty vector (pcDNA3.1/Zeo) or human MMP-14 cDNA (pcDNA3.1-MMP-14/Zeo). Cells were grown for 48 hours in monolayer culture. Cells were then lysed in TRIzol and total RNA was isolated. For each experimental condition, total RNAs isolated from 3 independant biological replicates were pooled.
2015-12-11 | E-GEOD-64320 | biostudies-arrayexpress
Project description:Matrix metalloprotease (MMP) -2 has been reported to be up-regulated in skeletal muscle in the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. However, the role of MMP-2 in dystrophin-deficient muscle is not well known. The aim of this study was to verify the role of MMP-2 in dystrophin-deficient muscle by using mdx mice with genetic ablation of MMP-2 (mdx/MMP-2-/-). Gene expression profiles were analyzed in the skeletal muscle of mdx and mdx/MMP-2-/- mice at 1 and 3 months of age. Tibialis anterior muscle was isolated from four groups of mice (mdx and mdx/MMP-2-/- mice at 1 and 3 months of age). Total RNA was purified and prepared for hybridization to Affymetrix Mouse Genome 430 2.0 arrays (Affymetrix Inc., Santa Clara, CA, USA) using Affymetrix reagents and protocols. The mRNA levels of differentially expressed genes from gene chip analysis were confirmed by quantitative real-time PCR assay.
2011-02-19 | E-GEOD-27129 | biostudies-arrayexpress