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Proteome profile of neutrophils from a transgenic diabetic pig model shows distinct changes.
J. Proteomics 224:103843 (2020)
INSC94Y transgenic pigs develop a stable diabetic phenotype early after birth and therefore allow studying the influence of hyperglycemia on primary immune cells in an early stage of diabetes mellitus in vivo. Since immune response is altered in diabetes mellitus, with deviant neutrophil function discussed as one of the possible causes in humans and mouse models, we investigated these immune cells in INSC94Y transgenic pigs and wild type controls at protein level. A total of 2371 proteins were quantified by label-free LC-MS/MS. Subsequent differential proteome analysis of transgenic animals and controls revealed clear differences in protein abundances, indicating a deviant behavior of granulocytes in the diabetic state. Interestingly, abundance of myosin regulatory light chain 9 (MLC-2C) was increased 5-fold in cells of diabetic pigs. MLC-2C directly affects cell contractility by regulating myosin ATPase activity, can act as transcription factor and was also associated with inflammation. It might contribute to impaired neutrophil cell adhesion, migration and phagocytosis.Our study provides novel insights into proteome changes in neutrophils from a large animal model for permanent neonatal diabetes mellitus and points to dysregulation of neutrophil function even in an early stage of this disease.Data are available via ProteomeXchange with identifier PXD017274.Significance: Our studies provide novel basic information about the neutrophil proteome of pigs and contribute to a better understanding of molecular mechanisms involved in altered immune cell function in an early stage diabetes. We demonstrate proteins that are dysregulated in neutrophils from a transgenic diabetic pig and have not been described in this context so far. The data presented here are highly relevant for veterinary medicine and have translational quality for diabetes in humans.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Quantitative Label-free Lc-ms/ms ; Diabetes Mellitus ; Neutrophil ; Granulocyte ; Transgenic Pig ; Myosin Regulatory Light Chain 9 (mlc-2c); Activation; Cells; Identification; Expression; Increases; Proteins; Alpha
ISSN (print) / ISBN
1874-3919
e-ISSN
1876-7737
Journal
Journal of Proteomics
Quellenangaben
Volume: 224,
Article Number: 103843
Publisher
Elsevier
Publishing Place
Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Metabolomics & Proteomics (CF-MPC)