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

Nat Commun. 2018 Sep 10;9(1):3660. doi: 10.1038/s41467-018-06094-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Movement
  • Chemokine CXCL12 / metabolism*
  • Energy Metabolism
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Glycolysis
  • Homeostasis
  • Kidney / injuries
  • Kidney / metabolism
  • Kidney Diseases / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • Tretinoin / chemistry
  • Zebrafish / genetics*
  • Zebrafish Proteins / metabolism*

Substances

  • Chemokine CXCL12
  • Proto-Oncogene Proteins
  • Zebrafish Proteins
  • cxcl12a protein, zebrafish
  • mycn protein, zebrafish
  • Tretinoin