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Proteomic Study of Low-Birth-Weight Nephropathy in Rats
- 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.
- Subjects :
- Male
Proteome
medicine.medical_treatment
030232 urology & nephrology
Mitochondrion
Oxidative Phosphorylation
Pathogenesis
Electron Transport Complex III
0302 clinical medicine
Focal segmental glomerulosclerosis
Pregnancy
Birth Weight
Biology (General)
Spectroscopy
0303 health sciences
Kidney
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
General Medicine
3. Good health
Computer Science Applications
mitochondria
Chemistry
Mitochondrial respiratory chain
medicine.anatomical_structure
nephropathy
Female
Kidney Diseases
medicine.drug
medicine.medical_specialty
kidney
NF-E2-Related Factor 2
QH301-705.5
Intraperitoneal injection
Biology
Article
Catalysis
Nephropathy
Inorganic Chemistry
03 medical and health sciences
proteomics
Internal medicine
medicine
Animals
low birth weight
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
Dexamethasone
030304 developmental biology
Organic Chemistry
Infant, Low Birth Weight
medicine.disease
Rats
Rapamycin-Insensitive Companion of mTOR Protein
Endocrinology
Animals, Newborn
Biomarkers
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
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