CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury

  • Kidney injury is a common complication of severe disease. Here, we report that injuries of the zebrafish embryonal kidney are rapidly repaired by a migratory response in 2-, but not in 1-day-old embryos. Gene expression profiles between these two developmental stages identify cxcl12a and myca as candidates involved in the repair process. Zebrafish embryos with cxcl12a, cxcr4b, or myca deficiency display repair abnormalities, confirming their role in response to injury. In mice with a kidney-specific knockout, Cxcl12 and Myc gene deletions suppress mitochondrial metabolism and glycolysis, and delay the recovery after ischemia/reperfusion injury. Probing these observations in zebrafish reveal that inhibition of glycolysis slows fast migrating cells and delays the repair after injury, but does not affect the slow cell movements during kidney development. Our findings demonstrate that Cxcl12 and Myc facilitate glycolysis to promote fast migratory responses during development and repair, and potentially also during tumor invasion and metastasis.
Author:Toma Yakulov, Abhijeet P. Todkar, Krasimir Slanchev, Johannes Wiegel, Alexandra Bona, Martin Groß, Alexander Scholz, Isabell Hess, Anne Wurditsch, Florian Grahammer, Tobias Huber, Virginie LecaudeyORCiDGND, Tillmann Bork, Jochen Hochrein, Melanie Börries, Justine Leenders, Pascal de Tullio, François Jouret, Albrecht Kramer-Zucker, Gerd Walz
Pubmed Id:
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/09/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/09/25
Tag:Developmental biology; Nephrons
Issue:1, Art. 3660
Page Number:15
First Page:1
Last Page:15
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Institutes:Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0