Dataset Information

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

ABSTRACT: 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.

OTHER RELATED OMICS DATASETS IN: PRJNA236469

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR)

SUBMITTER: Justine Leenders

PROVIDER: MTBLS723 | MetaboLights | 2018-10-11

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS723	Other
	FILES	Other
	a_MTBLS723_cxl12_-_myc_metabolite_profiling_NMR_spectroscopy.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS723_cxl12_-_myc_metabolite_profiling_NMR_spectroscopy_v2_maf.tsv	Tabular

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

Yakulov Toma A TA Todkar Abhijeet P AP Slanchev Krasimir K Wiegel Johannes J Bona Alexandra A Groß Martin M Scholz Alexander A Hess Isabell I Wurditsch Anne A Grahammer Florian F Huber Tobias B TB Lecaudey Virginie V Bork Tillmann T Hochrein Jochen J Boerries Melanie M Leenders Justine J de Tullio Pascal P Jouret François F Kramer-Zucker Albrecht A Walz Gerd G

Nature communications 20180910 1

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-spec ...[more]

PMID: 30202007

Similar Datasets

Project description:Injuries of the zebrafish kidney are rapidly repaired by a migratory response in two to three day-old embryos. While this migratory repair process re-establishes the integrity of the pronephric tubules independently of proliferation, fluid flow, intact cilia, or Wnt signaling, pronephros injuries before 36 hours post fertilization were repaired by a purse string-like mechanism that irreversibly occluded the pronephric tubules. Comparing the gene expression profiles between these two developmental stages and focusing on up-regulated zebrafish pronephros genes, we identified cxcl12a and myca as potential candidates orchestrating the migratory repair process. Zebrafish lines with either cxcl12a or cxcr4b mutations displayed striking repair abnormalities, confirming the requirement for cxc12a/cxcr4b signaling to override the ongoing collective cell migration and repair the pronephros injury. However, in contrast to the collective cell migration of the posterior lateral line primordium, cxc12a/cxcr4b signaling was dispensable for normal pronephros development. Zebrafish myca, the pronephros-specific homologue of human MYC, was also increased in cells participating in the repair response. The defective repair response caused by knockdown of myca resembled the abnormalities observed in cxcx12a/cxcr4b-deficient zebrafish, and was partially rescued by cxcr4b mRNA, suggesting that myca acts in part through up-regulating cxcr4b expression during the migration-based repair process. Kidney-specific knockout of Cxcl12 and Myc suppressed mitochondrial functions, reduced retinoic acid receptor signaling, and delayed the recovery after ischemic/reperfusion injury in mice. Tretinoin, known to stimulate Cxcr4 expression and mitochondrial metabolism, accelerated renal recovery. Thus, the zebrafish pronephros injury mode provides a systematic approach to identify molecules involved in the immediate repair response after kidney injury, and to design strategies to ameliorate this severe complication of human disease.