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Next generation sequencing and RNA-seq characterization of adipose tissue in the Nile crocodile (Crocodylus niloticus) in South Africa: Possible mechanism(s) of pathogenesis and pathophysiology of pansteatitis


Autoři: Odunayo I. Azeez aff001;  Jan G. Myburgh aff003;  Ana-Mari Bosman aff004;  Jonathan Featherston aff005;  Kgomotso P. Sibeko-Matjilla aff004;  Marinda C. Oosthuizen aff004;  Joseph P. Chamunorwa aff001
Působiště autorů: Anatomy and Physiology Dept., Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, South Africa aff001;  Dept. of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria aff002;  Paraclinical Science Dept., Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, South Africa aff003;  Veterinary Tropical Diseases Dept., Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, South Africa aff004;  Biotechnology Platform, Agricultural Research Council, Onderstepoort, Pretoria, South Africa aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225073

Souhrn

Background

Concerted efforts to identify the pathogenesis and mechanism(s) involved in pansteatitis, (a generalized inflammation of the adipose tissue), that was attributed to the recent crocodile die off in the Olifants River and Loskop Dam in Kruger National Park, Mpumalanga, South Africa have been in the forefront of research in recent time. As part of the efforts, molecular characterization of healthy and pansteatitis adipose tissue was carried out by RNA sequencing (RNA-Seq) using Next Generation Sequencing (NGS) and de novo assembly of the adipose transcriptome, followed by differential gene expression analysis.

Methodology

Healthy adipose tissue consisting of fifty samples was collected from the subcutaneous, visceral, intermuscular adipose tissues and the abdominal fat body of ten 4 years old juvenile crocodiles from a local crocodile farm in Pretoria, South Africa. Ten pansteatitis samples were collected from visceral and intermuscular adipose tissues of five crocodiles that were dying of pansteatitis.

Results

Forty-two thousand, two hundred and one (42,201) transcripts were assembled, out of which 37, 835 had previously been characterized. The de novo assembled transcriptome had an N50 (average sequence) of 436 bp, percentage GC content of 43.92, which compared well with previously assembled transcripts in the saltwater crocodile. Seventy genes were differentially expressed and upregulated in pansteatitis. These included genes coding for extracellular matrix (ECM) signaling ligands, inflammatory cytokines and tumour necrosis factor alpha (TNFα) receptors, fatty acid synthase and fatty acid binding proteins, peroxisome proliferator-activated receptor gamma (PPARγ), nuclear factor and apoptosis signaling ligands, and mitogen activated protein kinase enzymes among others. Majority (88.6%) of the upregulated genes were found to be involved in hypoxia inducible pathways for activation of NFkβ and inflammation, apoptosis, Toll-like receptor pathway and PPARγ. Bicaudal homologous 2 Drosophila gene (BICD2) associated with spinal and lower extremity muscle atrophy was also upregulated in pansteatitis while Sphingosine -1-phosphate phosphatase 2 (SGPP2) involved in Sphingosine -1- phosphate metabolism was downregulated. Futhermore, Doublesex–mab-related transcription factor 1 (DMRT1) responsible for sex gonad development and germ cell differentiation was also downregulated.

Conclusion

Thus, from the present study, based on differentially expressed genes in pansteatitis, affected Nile crocodiles might have died partly due to their inability to utilize stored triglycerides as a result of inflammation induced insulin resistance, leading to starvation in the midst of plenty. Affected animals may have also suffered muscular atrophy of the lower extremities and poor fertility.

Klíčová slova:

Adipose tissue – Apoptosis – Cytokines – Gene expression – Inflammation – Protein kinase signaling cascade – Transcriptome analysis – Crocodiles


Zdroje

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