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Shashikadze, B.* ; Flenkenthaler, F.* ; Kemter, E.* ; Franzmeier, S.* ; Stöckl, J.B.* ; Haid, M. ; Riols, F. ; Rothe, M.* ; Pichl, L.* ; Renner, S.* ; Blutke, A.* ; Wolf, E.* ; Fröhlich, T.*

Multi-omics analysis of diabetic pig lungs reveals molecular derangements underlying pulmonary complications of diabetes mellitus.

Dis. Model. Mech. 17:dmm050650 (2024)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal Disease Models and Mechanisms

Quellenangaben Volume: 17, Issue: 7, Article Number: dmm050650

Publisher Company of Biologists

Publishing Place Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)

Grants German Center for Diabetes Research (DZD e.V.)