Downregulation of miR-19a as a Biomarker for Early Detection of Silicosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80555 | GEO | 2016/04/22
SECONDARY ACCESSION(S): PRJNA319264
REPOSITORIES: GEO
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Project description:Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Using single-cell sequencing of bronchoalveolar lavage fluid (BALF) of mine workers with silicosis and their co-workers who did not develop silicosis, we found that the impaired interferon (IFN)-γ signaling in myeloid cells was strongly associated with the occurrence of silicosis. In a murine model of silicosis, global or myeloid cell-specific deletion of interferon γ receptor (IFN-γR) markedly enhanced the silica crystals-induced pulmonary interstitial fibrosis and respiratory dysfunction in wild-type but not in mutant mice deficient in NOD-like receptor family pyrin domain-containing 3 (NLRP3). In vitro, IFN-γ priming of macrophages suppressed the crystalline silica-induced NLRP3 inflammasome activation partly by inducing the formation of spacious phagosomes with relatively reduced ratio of crystalline silica/phagosomal areas/volumes through the RAB20-dependent membrane trafficking pathway. RAB20 deficiency was associated with the elevated susceptibility to silicosis as well as the elevated NLRP3 inflammasome activation in a manner similar to the impaired IFN-γ signaling. Thus, these findings provide novel molecular insights into the intricate mechanisms underlying innate immunity-mediated host responses to environmental irritants, and shed light on the future development of novel therapies for the prevention of silicosis.
2022-05-19 | GSE174725 | GEO
Project description:Silicosis, a fibrotic granulomatous lung disease, may occur through accidental high-dose or occupational inhalation of silica, leading to acute/accelerated and chronic silicosis, respectively. While chronic silicosis has a long asymptomatic latency, lung inflammation and apoptosis are hallmarks of acute silicosis. In animal models, histiocytic granulomas develop within days after high-dose intratracheal silica instillation. However, following chronic inhalation of occupationally relevant doses of silica, discrete granulomas resembling human silicosis arise months after the final exposure without significant lung inflammation/apoptosis. To identify molecular events associated with chronic silicosis, lung RNAs from controls or chronically silica-exposed rats were analyzed by Affymetrix at 28 wk after silica exposures. Results suggested a significant upregulation of 144 genes and downregulation of seven genes. The upregulated genes included complement cascade, chemokines/chemokine receptors, G-protein signaling components, metalloproteases, and genes associated with oxidative stress. To examine the kinetics of gene expression relevant to silicosis, qPCR, ELISA, Luminex-bead assays, Western blotting, and/or zymography were performed on lung tissues from 4 d, 28 wk, and intermediate times after chronic silica exposure and compared with 14 d acute silicosis samples. Results indicated that genes regulating fibrosis (secreted phosphoprotein-1, CCL2, and CCL7), redox enzymes (superoxide dismutase-2 and arginase-1), and the enzymatic activities of matrix metalloproteinases 2 and 9 were upregulated in acute and chronic silicosis; however, proinflammatory cytokines were strongly upregulated only in acute silicosis. Thus, inflammatory cytokines are associated with acute but not chronic silicosis; however, genes regulating fibrosis, oxidative stress, and metalloproteases may contribute to both acute and chronic silicosis.
2012-01-01 | GSE29110 | GEO
Project description:Silicosis, a fibrotic granulomatous lung disease, may occur through accidental high-dose or occupational inhalation of silica, leading to acute/accelerated and chronic silicosis, respectively. While chronic silicosis has a long asymptomatic latency, lung inflammation and apoptosis are hallmarks of acute silicosis. In animal models, histiocytic granulomas develop within days after high-dose intratracheal silica instillation. However, following chronic inhalation of occupationally relevant doses of silica, discrete granulomas resembling human silicosis arise months after the final exposure without significant lung inflammation/apoptosis. To identify molecular events associated with chronic silicosis, lung RNAs from controls or chronically silica-exposed rats were analyzed by Affymetrix at 28 wk after silica exposures. Results suggested a significant upregulation of 144 genes and downregulation of seven genes. The upregulated genes included complement cascade, chemokines/chemokine receptors, G-protein signaling components, metalloproteases, and genes associated with oxidative stress. To examine the kinetics of gene expression relevant to silicosis, qPCR, ELISA, Luminex-bead assays, Western blotting, and/or zymography were performed on lung tissues from 4 d, 28 wk, and intermediate times after chronic silica exposure and compared with 14 d acute silicosis samples. Results indicated that genes regulating fibrosis (secreted phosphoprotein-1, CCL2, and CCL7), redox enzymes (superoxide dismutase-2 and arginase-1), and the enzymatic activities of matrix metalloproteinases 2 and 9 were upregulated in acute and chronic silicosis; however, proinflammatory cytokines were strongly upregulated only in acute silicosis. Thus, inflammatory cytokines are associated with acute but not chronic silicosis; however, genes regulating fibrosis, oxidative stress, and metalloproteases may contribute to both acute and chronic silicosis. 3 rats were chronically exposed to silica by inhalation. Briefly, exposure chambers were maintained with an airflow rate of ~15 cfm and temperature range of 22‚Äì26¬?C. Animals were exposed to 6.2 mg/m3 aerosolized silica (Min-U-Sil 5; U.S. Silica, Mill Creek, OK) with an average particle size of 1.75 ¬± 0.05 mm (mass median aerodynamic diameter) 6 h/d, 5 d/wk (Monday‚ÄìFriday) for 6 wk. 3 control animals received filtered air under similar inhalation conditions.
2012-01-01 | E-GEOD-29110 | biostudies-arrayexpress
Project description:Atractylenolide III (ATL-III) is a major active constituent of the natural plant Atractylodes rhizome. Our previous study has shown that ATL-III may alleviate alveolar macrophage apoptosis via the inhibition of the mammalian target of rapamycin (mTOR)-mediated autophagy of human silicosis. Therefore, we aimed to further explore the function of ATL-III in autophagy, apoptosis, and pulmonary fibrosis by establishing the ATL-III-intervened silicosis mouse model in this study. Meanwhile, we sought and then verified potential autophagy-related signaling pathways by matching differentially expressed genes (attained by RNA sequencing) and the autophagy database. In this study, RNA-sequencing results implied that the epidermal growth factor receptor, the crucial upstream activator of mTOR, was seen as a potential autophagy-regulatory molecule in the ATL-IIIeintervened silicosis mouse model. The finding of this study was that ATL-III might improve the disorder of autophagic degradation via the activation of epidermal growth factor receptor-mTOR signals in the pulmonary tissue of the silicosis mouse model. ATL-III also alleviated cell apoptosis and silicotic fibrosis. Overall, we supposed that ATL-III might be a potential protective medicine, which had a regulatory effect on autophagy, for the intervention of silicotic fibrosis. In the future, the therapeutic drugs for silicosis should be further focused on the development and application of such natural autophagy agents.
2023-10-25 | GSE245655 | GEO
Project description:Pain management is an important issue in veterinary medicine, requiring biomarkers with high sensitivity and specificity for the timely and effective treatment. Emerging evidence suggests that miRNAs are promising pain-related markers. The aims were to profile the circulating miRNA signature in plasma of turtles (Trachemys scripta) and point out potential candidate biomarkers of pain. Plasma of female turtles underwent surgical gonadectomy were collected 24h pre-surgery, and 2.5h and 36 h post-surgery. The expression of miRNAs was profiled by Next Generation Sequencing and the dysregulated miRNAs were validated using RT-qPCR. The diagnostic value of miRNAs was calculated by ROC curves.
2021-07-28 | GSE175466 | GEO
Project description:Impaired interferon-γ signaling promotes the development of silicosis
| PRJNA731230 | ENA
Project description:Objective:This study aims to discover circulating exosomal miRNAs as potential noninvasive biomarkers early detection of fetus with ventricular septal defect (VSD). Method:A total of 182 pregnant women including 91 VSD cases and 91 matched controls were included in this study. Exosomes were isolated and next-generation sequencing was used to obtain a profile of dysregulated exosomal miRNA. The differential abundance was verified by quantitative real-time PCR (q RT-PCR). . Receiver operating characteristic (ROC) curves were conducted to evaluate the diagnostic accucary Results: 77 serum exosomal miRNA were uncovered to be differentially expressed in the VSD group as compared to the control group. Among these, five down-regulated exosomal miRNA were validated by qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSDs from controls (area under the ROC (AUC): 0.997; p < 2.2e-16). Conclusion: circulating exosomal miRNA, in particular, hsa-miR-146a-5pmay be a predictive biomarker for non-invasive prenatal diagnosis of fetal VSDs.
2021-06-05 | GSE176134 | GEO
Project description:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD DNA obtained from 164 AERD subjects, 397 subjects with aspirin-tolerant asthma (ATA), 398 normal controls and 10 null samples were subjected to Exome Chip assay of 240K SNPs. 1023 model (210-1) were generated from combination of the top 10 SNPs selected by p-values. The area under the curve (AUC) value of receiver operating characteristic (ROC) curves was calculated for each model. SNP functional Portal and PolyPhen-2 was used to validate the functional significance of the candidate SNPs
2014-09-05 | E-GEOD-61129 | biostudies-arrayexpress
Project description:In this study, we aimed to identify a miRNA expression signature that could be used to distinguish PCa from BPH. We have shown for the first time in the literature the presence of miRNAs in the PSS. We suggest PSS as a powerful non-invasive source for evaluation of prognosis in PCa, since prostate massages can be easily applied during routine examination. Our results showed that certain differentially expressed miRNAs in PSS could be used as diagnostics markers. Prostate secretion samples (PSS) from 23 PCa and 25 benign prostate hyperplasia (BPH) patients were obtained from Urology Department of Bagcilar Educational and Research Hospital (Istanbul). MicroRNA (miRNA) profiling of eight PSS (four from BPH, four from PCa patients) were performed using microarray. Four of significantly deregulated miRNAs were further confirmed using quantitative reverse-transcription PCR (qRT-PCR). Statistical analysis was performed using Student’s t-test. ROC curves were plotted with SPSS-15.0.
2013-09-27 | E-GEOD-49298 | biostudies-arrayexpress
Project description:CTCs in cancer patients are thought to be responsible for metastasis. Currently, there is no ex vivo model that can isolate this group of cells. We have developed an ex vivo 4D lung cancer model that forms perfusable tumor nodules and form CTCs. Gene array analyses show 2504 differentially expressed genes when comparing CTCs from the 4D model seeded with A549 cells to the same cells grown on a petri dish (2D). We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, human lung cancer cell line, grown on petri dish (2D) and same cells circulating as tumor cells in our ex vivo model (4D/CTC).
2015-03-12 | E-GEOD-50991 | biostudies-arrayexpress