Lung ischaemia–reperfusion induced gene expression

Ng, Calvin S.H.; Hui, Connie W. C.; Wan, Song; Wan, Innes Y.P.; Ho, Anthony M.‐H.; Lau, Kin Mang; Darzi, Ara; Underwood, Malcolm J.

doi:10.1016/j.ejcts.2010.01.001

Cited by 9 publications

(3 citation statements)

References 19 publications

(37 reference statements)

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“…This was confirmed at the protein level with an increase in LCN2 and a decrease in CXCL10 in mice subjected to hypoxia-reoxygenation. In concordance with these results, downregulation of inflammatory genes has been reported after ischemia-reperfusion in adult rats [16], while another study reported increased expression of inflammatory genes [11]. Previously, we have reported both unaltered [8] and increased inflammatory markers [7] after hypoxia-reoxygenation in neonatal pigs, and upregulated Lcn2 after hypoxia-reoxygenation in mice [9].…”

Section: Discussionsupporting

confidence: 75%

Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation

Rognlien

Wollen²,

Atneosen-Åsegg³

et al. 2016

Neonatology

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Background: One out of four children with neonatal asphyxia has lung involvement. Still, there has been little research on injury mechanisms of hypoxia-reoxygenation in the neonatal lung. Objectives: To make a temporal profile of the gene expression changes of 44 a priori selected genes after hypoxia-reoxygenation in the newborn mouse lung, and to compare the changes after hyperoxic and normoxic reoxygenation. Methods: Postnatal day 7 mice were randomized to 2-hour hypoxia (8% O₂) and 30-min reoxygenation in either 60% O₂ or air. After 0-72 h of observation, gene expression changes and protein concentrations in whole lung homogenates were examined. Results: Immediately after completed reoxygenation, 7 genes of mediators of inflammation were downregulated, and there was an antiapoptotic gene expression pattern. Three DNA glycosylases were downregulated, while genes involved in cell cycle renewal indicated both increased and decreased cell cycle arrest. Sod1 (T2.5h median H60: 1.01, H21: 0.88, p = 0.005; T5h median H60: 1.04, H21: 0.85, p = 0.038) and Il1b (T0h median H60: 0.86, H21: 1.08, p = 0.021) were significantly differentially expressed when comparing hyperoxic and normoxic reoxygenation. Conclusion: In this newborn mouse lung hypoxia-reoxygenation model, we found downregulation of genes of mediators of inflammation, an antiapoptotic gene expression pattern, and downregulation of DNA glycosylases. Sod1 and Il1b were significantly differentially expressed when comparing reoxygenation using 60% O₂ with air.

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Section: Discussionsupporting

confidence: 75%

Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation

Rognlien

Wollen²,

Atneosen-Åsegg³

et al. 2016

Neonatology

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“…PubMed was searched for all messenger RNA (mRNA) microarray studies describing significantly upregulated gene expression in nonfetal lung cells or tissue in the setting of ALI, acute respiratory distress syndrome, pulmonary ischemia‐reperfusion, and/or primary pulmonary graft dysfunction. A total of 31 gene lists including 843 unique genes were identified from 23 articles . Based on the experimental models used in each study, these gene lists were subdivided into one of 3 “mechanical/noninfectious” categories (ischemia‐reperfusion, stretch, primary graft dysfunction) or one of 3 “toxic/infectious” categories (infection, sepsis, toxicity).…”

Section: Methodsmentioning

confidence: 99%

“…Genome‐wide microarray studies have previously demonstrated that ALI induces coordinated changes in the expression of hundreds of genes . We hypothesized that analyzing a representative subset of these previously described ALI‐related transcripts would allow for more precise, objective, and mechanistic evaluation of lung tissue injury and repair before, during, and after EVLP.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs

Dromparis

Aboelnazar

Wagner

et al. 2019

American Journal of Transplantation

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Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex vivo repair remain poorly understood. We aimed to assess the utility of gene expression for characterizing ALI during EVLP. One hundred sixty-nine porcine lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11) hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12 (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies. The expression of 53 previously described ALI-related genes was measured and correlated with function and histology. Twenty-eight genes were significantly upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets demonstrated differential expression with EVLP (P < .001) but not CSP. Upregulated 28-gene set expression peaked after 6 hours of EVLP, whereas downregulated 6-gene set expression continued to decline after 12 hours. Cellular perfusates demonstrated a greater reduction in downregulated 6-gene set expression vs acellular perfusate (P < .038). Gene set expression correlated with relevant functional and histologic parameters, including P/F ratio (P < .001) and interstitial inflammation (P < .005). Further studies with posttransplant results are warranted to evaluate the clinical significance of this novel molecular approach for assessing organ quality during EVLP.

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Applications of transcriptomics in ischemia reperfusion research in lung transplantation

Jeon,

Rajapaksa,

Keshavjee

et al. 2024

The Journal of Heart and Lung Transplantation

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Lung ischaemia–reperfusion induced gene expression

Cited by 9 publications

References 19 publications

Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation

Temporal Patterns of Gene Expression Profiles in the Neonatal Mouse Lung after Hypoxia-Reoxygenation

Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs

Applications of transcriptomics in ischemia reperfusion research in lung transplantation

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