ScRNA-seq analysis of biopsy tissue from Interstitial Lung Disease patients who took EGCG
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE239664 | GEO | 2024/07/10
REPOSITORIES: GEO
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Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
2016-08-01 | E-GEOD-81292 | biostudies-arrayexpress
Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.
2016-08-01 | E-GEOD-81293 | biostudies-arrayexpress
Project description:Myofibroblasts are key effector cells in the extracellular matrix remodeling of systemic sclerosis-associated interstitial lung disease (SSc-ILD), however the diversity of fibroblast populations present in the healthy and SSc-ILD lung is unknown, and has prevented the specific study of the myofibroblast transcriptome. We sought to identify and define the transcriptomes of myofibroblasts and other mesenchymal cell populations in human healthy and SSc-ILD lungs to understand how alterations in fibroblast phenotypes lead to SSc-ILD fibrosis.
2019-08-14 | GSE128169 | GEO
Project description:Pulmonary fibrosis develops as a consequence of environmentally induced lung injury and/or an inherent disease susceptibility causing fibroblast activation, proliferation and extracellular matrix deposition. The study was undertaken to characterise global gene expression in pulmonary fibroblasts to better understand the mechanisms underlying the fibrotic fibroblast phenotype. Gene expression was evaluated in lung fibroblasts derived from ten controls (normal periphery of resected tumor), open lung biopsies from eight patients with interstitial lung disease associated with systemic sclerosis (fibrotic non specific interstitial pneumonia pattern on biopsy), and from three patients with usual interstitial pneumonia. Lung fibroblasts were grown to confluence in DMEM with 10% fetal calf serum. At confluence, lung fibroblasts were serum-deprived for 44 hours in the presence of fibroblast growth medium with the addition of 0.1% bovine serum albumin (Sigma).
2013-08-05 | E-GEOD-40839 | biostudies-arrayexpress
Project description:There is a pressing need to identify early biomarkers of lung involvement in systemic sclerosis (SSc) to start as soon as possible antifibrotic therapy. We aimed to identify extracellular vesicle-derived microRNAs (EV-miRNAs) that are differentially expressed between SSc patients with and without interstitial lung disease (ILD) and explore their diagnostic value. Small EVs derived from plasma were isolated from 20 well-characterised SSc patients with ILD (SSc-ILD, n=10), without ILD (SSc-no ILD, n=10) and 10 matched healthy subjects (HS). Small RNA sequencing was used to identify sEV-miRNAs associated to SSc-ILD.
2024-09-15 | E-MTAB-14290 | biostudies-arrayexpress
Project description:EGCG effect proteomic profiles of Streptococcus suis
2022-10-14 | PXD026047 | Pride
Project description:Fibrotic interstitial lung disease (ILD) are lung disorders characterized by the accumulation of extracellular matrix, ultimately resulting in the destruction of the pulmonary scaffold. Continuous pro-fibrotic signaling perpetuates the remodeling process, specifically targeting the epithelial cell compartment, thereby destroying the gas exchange area. Studies that address this detrimental crosstalk between lung epithelial cells and fibroblasts are key to understanding ILD. With the aim of identifying functionally relevant targets that drive mesenchymal-epithelial crosstalk and their potential as new avenues to therapeutic strategies, we developed an organoid co-culture system based on human induced pluripotent stem cell-derived alveolar epithelial type 2 cells and lung fibroblasts from ILD patients as well as IMR-90 controls. While organoid formation capacity and organoid size was comparable in the presence of ILD or control lung fibroblasts, metabolic activity was significantly increased in ILD co-cultures. Alveolar organoids cultured with ILD fibroblasts further demonstrated reduced stem cell function supported by reduced Surfactant Protein C gene expression together with an aberrant basaloid-prone differentiation program indicated by elevated Cadherin 2, Bone Morphogenic Protein 4 and Vimentin transcription. In order to identify key mediators of the misguided mesenchymal-to-epithelial crosstalk with a focus on disease-relevant inflammatory processes, we used secretome mass spectrometry to identify key signals secreted by end stage ILD lung fibroblasts. Over 2000 proteins were detected in a single-shot experiment with 47 differentially upregulated proteins when comparing ILD and non-chronic lung disease control fibroblasts. The secretome profile was dominated by chemokines of the C-X-C motif family, including CXCL1, -3, and -8, all interfering with (epithelial) growth factor signaling orchestrated by Interleukin 11 (IL11), steering fibrogenic cell-cell communication, and proteins regulating extracellular matrix remodeling including epithelial-to-mesenchymal transition. When in turn treating 3D monocultures of iAT2s with IL11 we recapitulated the co-culture results obtained with primary ILD fibroblasts including changes in metabolic activity as well as organoid formation capacity and size. In summary, our analysis identified mesenchyme-derived mediators likely contributing to the disease-perpetuating mesenchymal-to-epithelial crosstalk in ILD by using sophisticated alveolar organoid co-cultures indicating the importance of cytokine-driven aberrant epithelial differentiation and confirmed IL11 as a key player in ILD using an unbiased approach.
2023-04-19 | PXD039554 | Pride
Project description:Gene expression of human lung tissue bronchoalveolar lavage (BAL), whole tissue biopsy, and digested single cell suspension of lung tissue from control and ILD samples.
2021-03-08 | GSE166036 | GEO
Project description:In the current study, we investigated the modulatory effect of epigallocatechin gallate (EGCG, an active derivative of green tea) on cellular miRNA expression and cell cycle proliferation in NSCLCs (A549). As the IC50 value of EGCG is approximately 304 μM, our studies support the resistance of A549 lung cancer cell by EGCG. In addition, it was interesting to observe its G0/G1 cell cycle arrest activity at 40μM EGCG treatment. So, in the present study, next-generation sequencing (NGS) was used to study the miRNA expression between the cancer control and EGCG-treated samples. A549 cells were treated with 40 μM and 100 μM EGCG. NGS was employed to study the differential expression of novel and known miRNAs. The data generated was analysed with computational approach to study and correlate the expression profiles of both known and novel miRNAs. Differential expression of known miRNAs was observed between control and EGCG-treated samples. Some putative novel miRNA sequences were also observed in the current study. The differential expression levels of putative novel miRNA sequences were estimated by counting the number of reads in the given dataset. Together the analysis of these miRNA profiles revealed log2-fold modulation in the expression levels. We detected 344, 337, and 346 number of known mature miRNAs in control, 40 μM EGCG treated, and 100 μM EGCG treated samples, respectively. We also reported 119, 126, and 125 number of putative novel mature miRNA sequences in control, 40 μM EGCG treated, and 100 μM EGCG treated samples, respectively. In conclusion, the analysis demonstrates that EGCG is actively involved in miRNA modulation in NSCLCs, which further attests to its chemoprotective role and could play a major role in therapeutic applications.
2019-02-07 | GSE110514 | GEO
Project description:Overexpression of the epidermal growth factor receptor family member Her-2/neu in breast cancer leads to autophosphorylation of the receptor, and induction of multiple downstream signaling pathways including Akt kinase to NF-kappaB cascade that is associated with poor prognosis. Previously, we demonstrated green tea polyhenol epigallocatechin 3-gallate (EGCG) inhibits growth of NF639 Her-2/neu-driven breast cancer cells via reducing receptor autophosphorylation, and downstream Akt and NF-kappaB activities (Pianetti et al., 2002). Interestingly, we noted that upon prolonged culture in the presence of EGCG some cells developed resistance to the polyphenol. Here we report that resistant cells have lost tyrosine phosphorylation on the Her-2/neu receptor. Surprisingly, they displayed elevated NF-kappaB activity, and inhibition of this activity sensitized cells to EGCG. Data from microarray analysis of the original and resistant NF639 populations of cells were subjected to Gene Set Enrichment Analysis (GSEA) pathway analysis, which revealed that the mitogen activated protein kinase (MAPK) pathway was activated in the resistant cells. Treatment of the resistant cells with a combination of EGCG and the MAPK inhibitor U0216 dramatically reduced colony growth and mesenchymal phenotype. Thus, activation of the MAPK pathway mediates resistance to EGCG. Our studies suggest that gene expression profiling of drug resistant cells may provide a mechanism of determining effective systemic therapies for treatment of these advanced cancers. Keywords: Drug resistance
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