Identification of Key Pathways and Genes in the Progression of Silicosis Fibrosis Based on WGCNA
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ABSTRACT:
PROVIDER: PRJNA839386 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19270800_1.fastq.gz | Fastqsanger.gz | |||
| SRR19270800_2.fastq.gz | Fastqsanger.gz | |||
| SRR19270801_1.fastq.gz | Fastqsanger.gz | |||
| SRR19270801_2.fastq.gz | Fastqsanger.gz | |||
| SRR19270802_1.fastq.gz | Fastqsanger.gz |
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Project description:The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.
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Project description:The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.
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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.
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Project description:Background :Nitrogen (N) supply directly impacts growth and quality in flue-cured tobacco. To decipher molecular responses to N gradients, we integrated transcriptomics and weighted gene co-expression network analysis (WGCNA) on leaves from four N treatments: 0 (inherent soil fertility), 60 (low), 105 (standard), and 150 kg/hm² (high). Results :Phenotypic analysis revealed dose-dependent increases in leaf nitrogen content with higher N application, accompanied by excessive vegetative growth and delayed maturity at 150 kg/hm². Transcriptome sequencing identified 47,216 genes, with differentially expressed genes (DEGs) increasing linearly with N levels (1,458–2,147 DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment highlighted nitrogen metabolism pathways, yielding 14 DEGs (11 in assimilation, 3 in transport). Weighted gene co-expression network analysis (WGCNA) uncovered two modules (lightcyan1 and black) strongly associated with N responses, harboring transcription factors NtERF11 (AP2/ERF), NtWRKY3 (WRKY), and NtSRM1 (MYB). Sub-network analysis within these modules identified five hub genes: NtGLN1-1, two uncharacterized genes, NtDFC , and NtGDSL. NtGDSL may enhance nitrogen use efficiency (NUE) through stress-responsive mechanisms, while NtDFC could integrate N signaling with developmental processes. These findings provide novel insights into N regulatory networks in flue-cured tobacco. Conclusions :This study reveals the effects of nitrogen application rates on flue-cured tobacco growth and gene expression. By identifying key transcription factors and genes regulating nitrogen metabolism, it provides a theoretical basis for dissecting nitrogen regulatory mechanisms, optimizing fertilization strategies, and improving nitrogen use efficiency in tobacco production.
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Project description:BackgroundThe morbidity of nonalcoholic fatty liver disease (NAFLD) has been rising, but the pathogenesis of NAFLD is still elusive. This study is aimed at determining NAFLD-related hub genes based on weighted gene coexpression network analysis (WGCNA).MethodsGSE126848 dataset based construction of coexpression networks was performed based on WGCNA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hub genes were identified and validated in independent datasets and mouse model.ResultsWe found that the steelblue module was most significantly correlated with NAFLD. Total 15 hub genes (NDUFA9, UQCRQ, NDUFB8, COPS5, RPS17, UBL5, PSMA3, PSMA1, SF3B5, MRPL27, RPL26, PDCD5, PFDN6, SNRPD2, PSMB3) were derived from both the coexpression and PPI networks and considered "true" hub genes. Functional enrichment analysis showed that the hub genes were related to NAFLD pathway and oxidative phosphorylation. Independent dataset-based analysis and the establishment of NAFLD mouse model confirmed the involvement of two hub genes NDUFA9 and UQCRQ in the pathogenesis of NAFLD.ConclusionsOxidative phosphorylation and NAFLD pathway may be crucially involved in the pathogenesis of NAFLD, and two hub genes NDUFA9 and UQCRQ might be diagnostic biomarkers and therapeutic targets for NAFLD.
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