Dataset Information

Holistic proteome analyses of heart samples from GHR-deficient (GHR-KO) pigs

ABSTRACT: A proteomics analysis of heart samples from GH receptor deficient (GHR-KO) pigs has been performed. This animal model is unique to study consequences of lacking GH actions. In this study, we used LC-MS/MS to capture alterations in the heart proteome of this clinically relevant large animal model.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Heart

DISEASE(S): Laron Syndrome

SUBMITTER: Thomas Fröhlich

LAB HEAD: Thomas Fröhlich

PROVIDER: PXD019852 | Pride | 2020-12-01

REPOSITORIES: Pride

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Publications

Growth hormone receptor knockout to reduce the size of donor pigs for preclinical xenotransplantation studies.

Hinrichs Arne A Riedel Evamaria O EO Klymiuk Nikolai N Blutke Andreas A Kemter Elisabeth E Längin Matthias M Dahlhoff Maik M Keßler Barbara B Kurome Mayuko M Zakhartchenko Valeri V Jemiller Eva-Maria EM Ayares David D Bidlingmaier Martin M Flenkenthaler Florian F Hrabĕ de Angelis Martin M Arnold Georg J GJ Reichart Bruno B Fröhlich Thomas T Wolf Eckhard E

Xenotransplantation 20201125 2

<h4>Background</h4>Many genetically multi-modified donor lines for xenotransplantation have a background of domestic pigs with rapid body and organ growth. The intrinsic growth potential of porcine xeno-organs may impair their long-term function after orthotopic transplantation in non-human primate models. Since growth hormone is a major stimulator of postnatal growth, we deleted its receptor (GHR-KO) to reduce the size of donor pigs in one step.<h4>Methods</h4>Heart weight and proteome profile ...[more]

PMID: 33241624

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Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.

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