Strain-dependent lung transcriptomic differences in cigarette smoke and LPS models of lung injury in mice
| Autor: | Jamila H. Siamwala, Jim A. Mossman, Christoph Schorl, Diana Borgas, Pavlo Sakhatskyy, David M. Rand, Qing Lu, Sharon Rounds |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Physiological Genomics. |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00152.2022 |
| Popis: | Background Cigarette smoke exposure increases the risk of developing Acute Respiratory Distress Syndrome (ARDS) after a number of disparate insults 1-3. It is not known why some at risk individuals develop ARDS, while others do not. Based on our previous finding that smoke-exposed AKR mice were more susceptible to lipopolysaccharides (LPS)-induced Acute Lung Injury (ALI) than C57BL/6 mice4, we investigated strain-dependent lung transcriptomic responses to cigarette smoke exposure. Methods Eight week old male AKR and C57BL/6 mice were exposed to 3 weeks of room air (RA) or cigarette smoke (CS) for 6 hours per day, 4 days per week, followd by intra-tracheal instillation of LPS or normal saline (NS) and microarray analysis of lung homogenate gene expression. Other groups of AKR and C57 mice were similarly exposed to RA or CS for 6 weeks, followed by evaluation of lung mechanics, pathology, and gene expression. Results Transcriptomic analyses of lung homogenates show distinct strain dependent lung transcriptional responses to CS and LPS, with AKR mice having larger numbers of genes affected than similarly treated C57 mice, congruent with strain differences in physiologic and inflammatory parameters previously observed in LPS-induced ALI after CS priming. These results suggest that genetic differences may underlie differing susceptibility of smokers to ARDS and emphysema. Conclusions Strain-based differences in gene transcription contribute to CS and LPS induced lung injury. Implications There may be a genetic basis for smoking related susceptibility to lung injury. Clinicians should consider cigarette smoke exposure as a risk factor for ALI and ARDS. |
| Databáze: | OpenAIRE |
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