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Proteomic Study of Low-Birth-Weight Nephropathy in Rats

Authors :
Nivea Dias Amoedo
Didier Lacombe
Rodrigue Rossignol
Toshiyuki Imasawa
Stéphane Claverol
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM)
Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM)
Chiba University Hospital
Université de Bordeaux (UB)
Cellomet [CHU Pellegrin, Bordeaux]
CHU de Bordeaux Pellegrin [Bordeaux]
Admin, Oskar
Source :
International Journal of Molecular Sciences, Volume 22, Issue 19, International Journal of Molecular Sciences, MDPI, 2021, 22 (19), ⟨10.3390/ijms221910294⟩, International Journal of Molecular Sciences, Vol 22, Iss 10294, p 10294 (2021)
Publication Year :
2021
Publisher :
Multidisciplinary Digital Publishing Institute, 2021.

Abstract

International audience; The hyperfiltration theory has been used to explain the mechanism of low birth weight (LBW)-related nephropathy. However, the molecular changes in the kidney proteome have not been defined in this disease, and early biomarkers are lacking. We investigated the molecular pathogen-esis of LBW rats obtained by intraperitoneal injection of dexamethasone into pregnant animals. Nor-mal-birth-weight (NBW) rats were used as controls. When the rats were four weeks old, the left kidneys were removed and used for comprehensive label-free proteomic studies. Following uninephrectomy, all rats were fed a high-salt diet until 9 weeks of age. Differences in the molecular composition of the kidney cortex were observed at the early step of LBW nephropathy pathogenesis. Untargeted quantitative proteomics showed that proteins involved in energy metabolism, such as oxidative phosphorylation (OXPHOS), the TCA cycle, and glycolysis, were specifically downregu-lated in the kidneys of LBW rats at four weeks. No pathological changes were detected at this early stage. Pathway analysis identified NEFL2 (NRF2) and RICTOR as potential upstream regulators. The search for biomarkers identified components of the mitochondrial respiratory chain, namely, ubiquinol-cytochrome c reductase complex subunits (UQCR7/11) and ATP5I/L, two components of mitochondrial F1FO-ATP synthase. These findings were further validated by immunohistology. At later stages of the disease process, the right kidneys revealed an increased frequency of focal segmental glomerulosclerosis lesions, interstitial fibrosis and tubular atrophy. Our findings revealed proteome changes in LBW rat kidneys and revealed a strong downregulation of specific mitochon-drial respiratory chain proteins, such as UQCR7.

Details

Language :
English
ISSN :
14220067 and 16616596
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....6e5d134f4585b87b8ccc10074932c324
Full Text :
https://doi.org/10.3390/ijms221910294