| First Author | Mohr J | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 5 | Pages | 5887-5902 |
| PubMed ID | 30721632 | Mgi Jnum | J:291982 |
| Mgi Id | MGI:6447439 | Doi | 10.1096/fj.201801875RR |
| Citation | Mohr J, et al. (2019) IL-6/Smad2 signaling mediates acute kidney injury and regeneration in a murine model of neonatal hyperoxia. FASEB J 33(5):5887-5902 |
| abstractText | 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-beta [mothers against decapentaplegic homolog (Smad)2] signaling, increased inflammatory markers, disrupted mitochondrial biogenesis, and reduced tubular proliferation. Regenerative phase at P70 was characterized by tubular proliferation in WT but not in IL-6(-/-) mice. These data demonstrate that hyperoxia increases the risk of CKD through a novel IL-6-Smad2 axis. The amenability of these pathways to pharmacological approaches may offer new avenues to protect premature infants from CKD.-Mohr, J., Voggel, J., Vohlen, C., Dinger, K., Dafinger, C., Fink, G., Gobel, H., Liebau, M. C., Dotsch, J., Alejandre Alcazar, M. A. IL-6/Smad2 signaling mediates acute kidney injury and regeneration in a murine model of neonatal hyperoxia. |
