دورية أكاديمية

Circadian disruption dysregulates lung gene expression associated with inflammatory lung injury

التفاصيل البيبلوغرافية
العنوان: Circadian disruption dysregulates lung gene expression associated with inflammatory lung injury
المؤلفون: Casanova, Nancy G., De Armond, Richard L., Sammani, Saad, Sun, Xiaoguang, Sun, Belinda, Kempf, Carrie, Bime, Christian, Garcia, Joe G. N., Parthasarathy, Sairam
المصدر: Frontiers in Immunology ; volume 15 ; ISSN 1664-3224
بيانات النشر: Frontiers Media SA
سنة النشر: 2024
المجموعة: Frontiers (Publisher - via CrossRef)
مصطلحات موضوعية: Immunology, Immunology and Allergy
الوصف: Rationale Circadian systems drive the expression of multiple genes in nearly all cells and coordinate cellular-, tissue-, and system-level processes that are critical to innate immunity regulation. Objective We examined the effects of circadian rhythm disorganization, produced by light shift exposure, on innate immunity-mediated inflammatory lung responses including vascular permeability and gene expression in a C57BL/6J murine model of inflammatory lung injury. Methods A total of 32 C57BL/6J mice were assigned to circadian phase shifting (CPS) with intratracheal phosphate-buffered saline (PBS), CPS with intratracheal lipopolysaccharide (LPS), control (normal lighting) condition with intratracheal PBS, and control condition with intratracheal LPS. Bronchoalveolar lavage (BAL) protein, cell counts, tissue immunostaining, and differentially expressed genes (DEGs) were measured in lung tissues at 2 and 10 weeks. Measurements and results In mice exposed to both CPS and intratracheal LPS, both BAL protein and cell counts were increased at both 2 and 10 weeks compared to mice exposed to LPS alone. Multiple DEGs were identified in CPS–LPS-exposed lung tissues compared to LPS alone and were involved in transcriptional pathways associated with circadian rhythm disruption, regulation of lung permeability, inflammation with Rap1 signaling, and regulation of actin cytoskeleton. The most dysregulated pathways included myosin light chain kinase, MAP kinase, profilin 2, fibroblast growth factor receptor, integrin b4, and p21-activated kinase. Conclusion Circadian rhythm disruption results in exacerbated immune response and dysregulated expression of cytoskeletal genes involved in the regulation of epithelial and vascular barrier integrity—the mechanistic underpinnings of acute lung injury. Further studies need to explore circadian disorganization as a druggable target.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
DOI: 10.3389/fimmu.2024.1348181
DOI: 10.3389/fimmu.2024.1348181/full
الإتاحة: https://doi.org/10.3389/fimmu.2024.1348181Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.5F428865
قاعدة البيانات: BASE