IL-6/Smad2 signaling mediates acute kidney injury and regeneration in a murine model of neonatal hyperoxia

2019 
Prematurity is linked to incomplete nephrogenesis and risk of chronic kidney diseases (CKDs). Oxygen is life-saving in that context but induces injury in numerous organs. Here, we studied the structural and functional impact of hyperoxia on renal injury and its IL-6 dependency. Newborn wild-type (WT) and IL-6 knockout (IL-6−/−) mice were exposed to 85% O2 for 28 d, followed by room air until postnatal d (P) 70. Controls were in room air throughout life. At P28, hyperoxia reduced estimated kidney cortex area (KCA) in WT; at P70, KCA was greater, number of glomeruli was fewer, fractional potassium excretion was higher, and glomerular filtration rate was slightly lower than in controls. IL-6−/− mice were protected from these changes after hyperoxia. Mechanistically, the acute renal injury phase (P28) showed in WT but not in IL-6−/− mice an activation of IL-6 (signal transducer and activator of transcription 3) and TGF-β [mothers against decapentaplegic homolog (Smad)2] signaling, increased inflammatory marke...
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