Interleukin‐36α as a potential biomarker for renal tubular damage induced by dietary phosphate load

Autor: Makoto Kuro-o, Kazuhiro Shiizaki, Yoshitaka Iwazu, Yoshitaka Hirano, Hiroshi Kurosu, Shuichi Tsuruoka
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Gene Expression
Inflammation
Nephron
Lipocalin
Kidney
General Biochemistry
Genetics and Molecular Biology
phosphate excretion per nephron
Proinflammatory cytokine
Phosphates
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
Interleukin-1alpha
interleukin‐36
Medicine
Animals
Osteopontin
lcsh:QH301-705.5
Research Articles
biology
business.industry
Interleukins
Acute kidney injury
Acute Kidney Injury
medicine.disease
dietary phosphate load
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Kidney Tubules
lcsh:Biology (General)
030220 oncology & carcinogenesis
Dietary Supplements
biology.protein
Cytokines
medicine.symptom
business
renal tubular damage
Biomarkers
Kidney disease
Research Article
Signal Transduction
Zdroj: FEBS Open Bio
FEBS Open Bio, Vol 10, Iss 5, Pp 894-903 (2020)
ISSN: 2211-5463
Popis: Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate‐induced kidney damage remain to be identified. Our previous RNA sequencing analysis of renal gene expression identified interleukin‐36α (IL‐36α) as a gene significantly upregulated by dietary phosphate load in mice. To determine the time course and dose dependency of renal IL‐36α expression induced by dietary phosphate load, we placed mice with or without uninephrectomy on a diet containing either 0.35%, 1.0%, 1.5%, or 2.0% inorganic phosphate for 10 days, 4 weeks, or 8 weeks and evaluated renal expression of IL‐36α and other markers of tubular damage and inflammation by quantitative RT‐PCR, immunoblot analysis, and immunohistochemistry. We found that IL‐36α expression was induced in distal convoluted tubules and correlated with phosphate excretion per nephron. The increase in IL‐36α expression was simultaneous with but more robust in amplitude than the increase in tubular damage markers such as Osteopontin and neutrophil gelatinase‐associated lipocalin, preceding the increase in expression of other inflammatory cytokines, including transforming growth factor‐α, interleukin‐1β, and transforming growth factor‐β1. We conclude that IL‐36α serves as a marker that reflects the degree of phosphate load excreted per nephron and of associated kidney damage.
An increase in dietary phosphate intake triggers renal tubular damage, followed by interstitial inflammation and fibrosis. Among several molecular markers indicative of these pathological changes, we identified induction of interleukin‐36α expression in distal tubules as an early and robust biomarker of phosphate‐induced tubular damage in mice.
Databáze: OpenAIRE
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