Timecourse on primary human highly differentiated airway epithelial cells infected with HRV-C15
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Cultured Cells
PROVIDER: ST001774 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Acute kidney injury is associated with mortality in COVID-19 patients. However, host cell changes underlying infection of renal cells with SARS-CoV-2 remain unknown and prevent understanding of the molecular mechanisms that may contribute to renal pathology. Here, we carried out quantitative translatome and whole-cell proteomics analyses of primary renal proximal and distal tubular epithelial cells derived from human donors infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type-specific changes over time. Our findings revealed shared pathways modified upon infection with both viruses, as well as SARS-CoV-2-specific host cell modulation driving key changes in innate immune activation and cellular protein quality control. Notably, MERS-CoV infection-induced specific changes in mitochondrial biology that were not observed in response to SARS-CoV-2 infection. Furthermore, we identified extensive modulation in pathways associated with kidney failure that changed in a virus- and cell type-specific manner. In summary, we provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary renal epithelial cells revealing key pathways that may be essential for viral replication.
| S-EPMC8814637 | biostudies-literature
Project description:Coronaviruses such as MERS-CoV and SARS-CoV-2 infect the human respiratory tract and can cause severe pneumonia. Disease severity and outcomes are different for these two infections: the human mortality rate for MERS-CoV and SARS-CoV-2 is over 30% and less than 10%, respectively. Here, using microarray assay, we analyzed the global alterations in gene expression induced by MERS-CoV or SARS-CoV-2 infections in primary human pulmonary epithelial cells. Overall, the number of differentially expressed genes was higher in human lung cells infected with MERS-CoV than in cells with SARS-CoV-2. Out of 44,556 genes analyzed, 127 and 50 were differentially expressed in cells infected with MERS-CoV and SARS-CoV-2, respectively (> 2-fold increase, compared to uninfected cells). Of these, only eight genes, including the one coding for CXCL8, were similarly modulated (upregulated or downregulated) by the two coronaviruses. Importantly, these results were virus-specific and not conditioned by differences in viral load, and viral growth curves were similar in human lung cells infected with both viruses. Our results suggest that these distinct gene expression profiles, detected early after infection by these two coronaviruses, may help us understand the differences in clinical outcomes of MERS-CoV and SARS-CoV-2 infections.
| S-EPMC7348575 | biostudies-literature
Project description:BackgroundProstate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men worldwide. Chromosomal instability (CIN) and polyploid giant cancer cells (PGCCs) have been considered predominant hallmarks of cancer. Recent clinical studies have proven the association of CIN, aneuploidy, and PGCCs with poor prognosis of prostate cancer (PCa). Evidence of HCMV transforming potential might indicate that HCMV may be involved in PCa.MethodsHerein, we underline the role of the high-risk HCMV-DB and -BL clinical strains in transforming prostate epithelial cells and assess the molecular and cellular oncogenic processes associated with PCa.ResultsOncogenesis parallels a sustained growth of "CMV-Transformed Prostate epithelial cells" or CTP cells that highly express Myc and EZH2, forming soft agar colonies and displaying stemness as well as mesenchymal features, hence promoting EMT as well as PGCCs and a spheroid appearance.ConclusionsHCMV-induced Myc and EZH2 upregulation coupled with stemness and EMT traits in IE1-expressing CTP might highlight the potential role of HCMV in PCa development and encourage the use of anti-EZH2 and anti-HCMV in PCa treatment.
| S-EPMC10604969 | biostudies-literature
Project description:Acute kidney injury is strongly associated with mortality in COVID-19 patients. However, host cell changes underlying infection of kidney cells with SARS-CoV-2 remain unknown and prevent understanding of the mechanisms leading to renal pathology. Here, we carried out extensive, dual-level proteomic analyses of primary human kidney cells infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type specific changes. We established cellular infection models of proximal and distal tubular epithelial cells derived from human donors. Infected cells were analyzed by quantitative translatome and whole-cell proteomics over time. Our findings reveal shared pathways modified upon infection with both viruses, as well as SARS-CoV-2 specific host cell modulation driving key changes in innate immune activation, cellular protein quality control and mitochondrial biology. In addition, we identified extensive modulation in pathways associated with kidney failure that were instinctively regulated in a virus- and cell type-specific manner. Our findings provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary kidney cells revealing key pathways and highlighting potential treatment options.
2022-01-30 | PXD024398 | Pride
Project description:The oral epithelium, the most abundant structural tissue lining the oral mucosa, is an important line of defense against infectious microorganisms. HIV infected subjects on highly active antiretroviral therapy (HAART) are susceptible to comorbid viral, bacterial and fungal infections in the oral cavity. To provide an assessment of the molecular alterations of oral epithelia potentially associated with susceptibility to comorbid infections in such subjects, we performed various proteomic studies on over twenty HIV infected and healthy subjects. In a discovery phase two Dimensional Difference Gel Electrophoresis (2-D DIGE) analyses of human oral gingival epithelial cell (HOEC) lysates were carried out; this identified 61 differentially expressed proteins between HIV-infected on HAART subjects and healthy controls. Down regulated proteins in HIV-infected subjects include proteins associated with maintenance of protein folding and pro- and anti-inflammatory responses (e.g., heat-shock proteins, Cryab, Calr, IL-1RA, and Galectin-3-binding protein) as well as proteins involved in redox homeostasis and detoxification (e.g., Gstp1, Prdx1, and Ero1). Up regulated proteins include: protein disulfide isomerases, proteins whose expression is negatively regulated by Hsp90 (e.g., Ndrg1), and proteins that maintain cellular integrity (e.g., Vimentin). In a verification phase, proteins identified in the protein profiling experiments and those inferred from Ingenuity Pathway Analysis were analyzed using Western blotting analysis on separate HOEC lysate samples, confirming many of the discovery findings. Additionally in HIV-infected patient samples Heat Shock Factor 1 is down regulated, which explains the reduced heat shock responses, while activation of the MAPK signal transduction cascade is observed. Overall, HAART therapy provides an incomplete immune recovery of the oral epithelial cells of the oral cavity for HIV-infected subjects, and the toxic side effects of HAART and/or HIV chronicity silence expression of multiple proteins that in healthy subjects function to provide robust innate immune responses and combat cellular stress.
| S-EPMC3218055 | biostudies-literature
Project description:Human cytomegalovirus is being recognized as a potential oncovirus beside its oncomodulation role. We previously isolated two clinical isolates, HCMV-DB (KT959235) and HCMV-BL (MW980585), which in primary human mammary epithelial cells promoted oncogenic molecular pathways, established anchorage-independent growth in vitro, and produced tumorigenicity in mice models, therefore named high-risk oncogenic strains. In contrast, other clinical HCMV strains such as HCMV-FS, KM, and SC did not trigger such traits, therefore named low-risk oncogenic strains. In this study, we compared high-risk oncogenic HCMV-DB and BL strains (high-risk) with low-risk oncogenic strains HCMV-FS, KM, and SC (low-risk) additionally to the prototypic HCMV-TB40/E, knowing that all strains infect HMECs in vitro. Numerous pro-oncogenic features including enhanced expression of oncogenes, cell survival, proliferation, and epithelial-mesenchymal transition genes were observed with HCMV-BL. In vitro, mammosphere formation was observed only in high-risk strains. HCMV-TB40/E showed an intermediate transcriptome landscape with limited mammosphere formation. Since we observed that Ki67 gene expression allows us to discriminate between high and low-risk HCMV strains in vitro, we further tested its expression in vivo. Among HCMV-positive breast cancer biopsies, we only detected high expression of the Ki67 gene in basal tumors which may correspond to the presence of high-risk HCMV strains within tumors. Altogether, the transcriptome of HMECs infected with HCMV clinical isolates displays an "oncogenic gradient" where high-risk strains specifically induce a prooncogenic environment which might participate in breast cancer development.
| S-EPMC8727587 | biostudies-literature
Project description:Human cytomegalovirus (HCMV) infection has been implicated in epithelial ovarian cancer (OC). Polyploidy giant cancer cells (PGCCs) have been observed in high-grade serous ovarian carcinoma (HGSOC); they possess cancer stem cell-like characteristics and give rise to progeny cells expressing epithelial-mesenchymal transition (EMT) markers. EZH2 plays a potential oncogenic role, correlating with high proliferative index and tumor grade in OC. Herein, we present the experimental evidence for HCMV as a reprogramming vector that elicited human ovarian epithelial cells (OECs) transformation leading to the generation of "CMV-transformed Ovarian cells" (CTO). The infection with the two high-risk clinical strains, namely HCMV-DB and BL provoked a distinct cellular and molecular mechanisms in infected OECs. EZH2 upregulation and cellular proliferation were curtailed by using EZH2 inhibitors. The HGSOC biopsies were characterized by an elevated EZH2 expression, possessing a strong positive correlation between the aforementioned marker and HCMV. From HGSOC biopsies, we isolated three HCMV clinical strains that transformed OECs generating CTO cells which displayed proliferative potentials in addition to EZH2 upregulation and PGCCs generation; these features were reduced upon EZH2 inhibition. High-risk HCMV strains transformed OECs confirming an HCMV-induced epithelial ovarian cancer model and highlighting EZH2 tumorigenic properties. Our findings might be highly relevant in the pathophysiology of ovarian tumors thereby nominating new targeted therapeutics.
| S-EPMC10555822 | biostudies-literature
Project description:Wounding of the oral mucosa occurs frequently in a highly septic environment. Remarkably, these wounds heal quickly and the oral cavity, for the most part, remains healthy. Deciphering the normal human oral epithelial cell (NHOEC) proteome is critical for understanding the mechanism(s) of protection elicited when the mucosal barrier is intact, as well as when it is breached. Combining 2D gel electrophoresis with shotgun proteomics resulted in identification of 1662 NHOEC proteins. Proteome annotations were performed based on protein classes, molecular functions, disease association and membership in canonical and metabolic signaling pathways. Comparing the NHOEC proteome with a database of innate immunity-relevant interactions (InnateDB) identified 64 common proteins associated with innate immunity. Comparison with published salivary proteomes revealed that 738/1662 NHOEC proteins were common, suggesting that significant numbers of salivary proteins are of epithelial origin. Gene ontology analysis showed similarities in the distributions of NHOEC and saliva proteomes with regard to biological processes, and molecular functions. We also assessed the interindividual variability of the NHOEC proteome and observed it to be comparable with other primary cells. The baseline proteome described in this study should serve as a resource for proteome studies of the oral mucosa, especially in relation to disease processes.
| S-EPMC3508721 | biostudies-literature
Project description:Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions but can be disturbed by environmental exposures. The mechanism(s) underlying the induction and impact of OS on airway epithelium and how these influences on respiratory disease is poorly understood. The aim of this study was to develop a stress response model in primary human nasal epithelial cells (NECs) grown at the air-liquid interface (ALI) into a well-differentiated epithelium and to use this model to investigate the mechanisms underlying OS. Hydrogen peroxide (H2O2) was used to induce acute OS and the responses were measured with trans epithelial electrical resistance (TEER), membrane permeability, cell death (LDH release), mitochondrial reactive oxygen species (mtROS) generation, redox status (GSH/GSSG ratio), cellular ATP, and signaling pathways (SIRT1, FOXO3, p53, p21, PINK1, PARKIN, NRF2). Following 25 mM (sensitive) or 50mM (resistant) H2O2 exposure, cell integrity decreased (p<0.05), GSH/GSSG ratio reduced (p<0.05), and ATP production declined by 83% (p<0.05) in the sensitive and 55% (p<0.05) in the resistant group; mtROS production increased 3.4-fold (p<0.001). Significant inter-individual differences between healthy humans with regards to susceptibility to OS, and differential activation of various pathways (FOXO3, PARKIN) were observed. These intra-individual differences in susceptibility to OS may be attributed to resistant individuals having more mitochondria or greater mitochondrial function.
| S-EPMC9912202 | biostudies-literature
Project description:We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.
| S-EPMC4582177 | biostudies-literature