Universität zu Köln

Mohr, Jasmine, Voggel, Jenny ORCID: 0000-0001-9120-2203, Vohlen, Christina, Dinger, Katharina, Dafinger, Claudia, Fink, Gregor ORCID: 0000-0001-7042-1706, Goebel, Heike, Liebau, Max C., Doetsch, Joerg and Alcazar, Miguel A. Alejandre (2019). IL-6/Smad2 signaling mediates acute kidney injury and regeneration in a murine model of neonatal hyperoxia. Faseb J., 33 (5). S. 5887 - 5903. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1530-6860

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Abstract

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% O-2 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- [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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mohr, Jasmine UNSPECIFIED UNSPECIFIED UNSPECIFIED Voggel, Jenny UNSPECIFIED orcid.org/0000-0001-9120-2203 UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dafinger, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gregor UNSPECIFIED orcid.org/0000-0001-7042-1706 UNSPECIFIED Goebel, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebau, Max C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-149470
DOI:	10.1096/fj.201801875RR
Journal or Publication Title:	Faseb J.
Volume:	33
Number:	5
Page Range:	S. 5887 - 5903
Date:	2019
Publisher:	FEDERATION AMER SOC EXP BIOL
Place of Publication:	BETHESDA
ISSN:	1530-6860
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRAUTERINE GROWTH RESTRICTION; YOUNG-ADULT AGE; OXIDATIVE STRESS; PRETERM INFANTS; RENAL-FUNCTION; RISK-FACTORS; FACTOR-BETA; INTERLEUKIN-6; BIRTH; EXPRESSION Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14947