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Multi-omics analysis of diabetic pig lungs reveals molecular derangements underlying pulmonary complications of diabetes mellitus.
Dis. Model. Mech. 17:dmm050650 (2024)
Growing evidence shows that the lung is an organ prone to injury by diabetes mellitus. However, the molecular mechanisms of these pulmonary complications have not yet been characterized comprehensively. To systematically study the effects of insulin deficiency and hyperglycaemia on the lung, we combined proteomics and lipidomics with quantitative histomorphological analyses to compare lung tissue samples from a clinically relevant pig model for mutant INS gene induced diabetes of youth (MIDY) with samples from wild-type (WT) littermate controls. Among others, the level of pulmonary surfactant-associated protein A (SFTPA1), a biomarker of lung injury, was moderately elevated. Furthermore, key proteins related to humoral immune response and extracellular matrix (ECM) organization were significantly altered in abundance. Importantly, a lipoxygenase pathway was dysregulated as indicated by a 2.5-fold reduction of polyunsaturated fatty acid lipoxygenase ALOX15 levels, associated with corresponding changes in the levels of lipids influenced by this enzyme. Our multi-omics study points to an involvement of reduced ALOX15 levels and an associated lack of eicosanoid switching as mechanisms contributing to a proinflammatory milieu in the lungs of subjects suffering from diabetes mellitus.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Biobank ; Diabetes ; Insulin Deficiency ; Lipidome ; Lipoxygenase ; Lung ; Pig Model ; Proteome; A Sp-a; Porcine Lung; Surfactant; Model; Proteoglycans; Biglycan; Insulin; Type-1; Tissue
ISSN (print) / ISBN
1754-8403
e-ISSN
1754-8411
Zeitschrift
Disease Models and Mechanisms
Quellenangaben
Band: 17,
Heft: 7,
Artikelnummer: dmm050650
Verlag
Company of Biologists
Verlagsort
Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CF Metabolomics & Proteomics (CF-MPC)
Förderungen
German Center for Diabetes Research (DZD e.V.)