Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: implications for research and diagnostics [EMC data]
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PROVIDER: PRJNA951627 | ENA |
REPOSITORIES: ENA
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Project description:Background & Aims: Cellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter transcriptome profiles. We have investigated this effect to obtain insight into molecular ischemia responses during surgical procedures and characterize pre-analytical effects impacting on molecular analyses. Methods: 143 non-malignant liver samples were obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts, treated either with the Pringle maneuver or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-qPCR. Results: Transcriptional profiles of both cohorts displayed 179 genes that were mutually deregulated confirming elevated cytokine signaling, and NFkB as the dominant pathways in ischemia response. Contrary to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NFkB and MAPK pathways. FOS and JUN were down-regulated in steatosis compared to their up-regulation in normal livers. Surprisingly, molecular signatures of underlying primary and secondary cancers were clearly present in the non-tumor tissue. Conclusions: We identified transcripts mutually deregulated during ischemia and reperfusion injury in both cohorts that can be used to monitor ischemia during liver surgery and highlight the importance of pre-analytical quality control. The marked inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a comprehensive and pre-analytically highly standardized in vivo transcriptome profile of histologically normal liver and identified 230 genes with substantial pre-analytical robustness (<2 % covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications. Conclusions: We identified transcripts mutually deregulated during ischemia and reperfusion injury in both cohorts that can be used to monitor ischemia during liver surgery and highlight the importance of pre-analytical quality control. The marked inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a comprehensive and pre-analytically highly standardized in vivo transcriptome profile of histologically normal liver and identified 230 genes with substantial pre-analytical robustness (<2 % covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications.
2024-02-21 | GSE228781 | GEO
Project description:Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: implications for research and diagnostics
| PRJNA951623 | ENA
Project description:Background & Aims: Cellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter transcriptome profiles. We have investigated this effect to obtain insight into molecular ischemia responses during surgical procedures and characterize pre-analytical effects impacting on molecular analyses. Methods: 143 non-malignant liver samples were obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts, treated either with the Pringle maneuver or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-qPCR. Results: Transcriptional profiles of both cohorts displayed 179 genes that were mutually deregulated confirming elevated cytokine signaling, and NFkB as the dominant pathways in ischemia response. Contrary to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NFkB and MAPK pathways. FOS and JUN were down-regulated in steatosis compared to their up-regulation in normal livers. Surprisingly, molecular signatures of underlying primary and secondary cancers were clearly present in the non-tumor tissue. Conclusions: We identified transcripts mutually deregulated during ischemia and reperfusion injury in both cohorts that can be used to monitor ischemia during liver surgery and highlight the importance of pre-analytical quality control. The marked inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a comprehensive and pre-analytically highly standardized in vivo transcriptome profile of histologically normal liver and identified 230 genes with substantial pre-analytical robustness (<2 % covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications. Conclusions: We identified transcripts mutually deregulated during ischemia and reperfusion injury in both cohorts that can be used to monitor ischemia during liver surgery and highlight the importance of pre-analytical quality control. The marked inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a comprehensive and pre-analytically highly standardized in vivo transcriptome profile of histologically normal liver and identified 230 genes with substantial pre-analytical robustness (<2 % covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications.
2024-02-21 | GSE228782 | GEO
Project description:Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: implications for research and diagnostics [MUG data]
| PRJNA951628 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-02-21 | GSE228783 | GEO
Project description:Structure formation of membrane proteins is error-prone and thus requires chaperones that oversee this essential process in cell biology. The ER membrane protein complex (EMC) is well-defined as a transmembrane domain (TMD) integrase. In this study, we characterize an additional chaperone function of the EMC. We use interactomics and systematic studies with model proteins to comprehensively define client features for this EMC chaperone mode. Based on this data, we develop a machine learning tool for client prediction. Mechanistically, our study reveals that the EMC engages TMDs via its EMC1 subunit and modulates their orientation within the lipid bilayer. Productive TMD assembly reduces binding to the EMC chaperone site. Taken together, our study provides detailed insights into an EMC chaperone function, further establishing the role of the EMC as a multifunctional molecular machine in membrane protein biogenesis.
2025-08-25 | PXD059792 | Pride
Project description:Microarray analysis of peripheral blood mononuclear cells (PBMCs), lungs, and lung lesions collected over the course of hCoV-EMC infection of 6 rhesus macaques.
2013-08-29 | GSE44542 | GEO
Project description:Ischemia-reperfusion (IR) injury, a ubiquitous consequence of liver transplantation, is a cause of early graft rejection and increased morbidity. At present, there are no effective strategies to reduce hepatic IR injury. Molecular mechanisms that promote cell survival under these circumstances are largely undefined. We examined changes in global gene expression at early reperfusion times to identify potential IR-mediated protective responses. Using a rat model of 30 minutes of 70% warm ischemia followed by reperfusion, RNA for microarray analysis was extracted from the non-ischemic and the ischemic-reperfused lobes at four reperfusion times: 0 (no reperfusion), 0.5, 2, and 6 hours. Differentially expressed genes and pathway analyses were used to identify IR-induced events. The transcriptome of the reperfused lobes was unique and discrete at each reperfusion time, showing no evidence of sustained changes of the gene expression alterations seen at 30 minutes of reperfusion. At all reperfusion times, a significant portion of gene expression changes in the reperfused lobes were present in the non-ischemic lobes. However, the earliest reperfusion time, 30 minutes, showed a marked increase in the expression of a set of immediate-early genes (c-Fos, c-Jun, Atf3, Egr1) that was exclusive to the reperfused lobe. Similarities of gene expression changes in the reperfused and the non-ischemic lobes at each time suggest that hemodynamics and/or circulating factors are potent stimuli in an IR model. However, early reperfusion events appear to reflect a cell-autonomous response that may be protective, thereby representing potential targets to ameliorate IR injury.
2019-12-16 | GSE117915 | GEO
Project description:Time course experiments involving bilateral renal ischemia reperfusion injury (IRI) in C57BL/6J mice (0 hr control, 20 min bilateral ischemia without reperfusion, 4, 16, 24, 36, 48, and 72 hrs post IRI). This dataset also includes IRI at 48 hrs and 72 hrs in Azin1 A-to-I locked and Azin1 A-to-I uneditable mice.
2024-09-30 | GSE267650 | GEO
Project description:Microarray analysis of peripheral blood mononuclear cells (PBMCs), lungs, and lung lesions collected over the course of hCoV-EMC infection of 6 rhesus macaques. 6 rhesus macaques were infected intratracheally with hCoV-EMC. PBMCs were collected at days 0, 1, 3, and 6, and lungs were collected from serial sacrifices of 3 animals each at day 3 and day 6. Infection produced a mild-moderate, self-limiting respiratory infection, and was not lethal. We performed microarray analysis (using Agilent Rhesus arrays) on all lungs, lung lesions, and PBMCs collected for the study.
2013-08-29 | E-GEOD-44542 | biostudies-arrayexpress