PUBLICATION

Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKI

Authors
Chiba, T., Skrypnyk, N.I., Skvarca, L.B., Penchev, R., Zhang, K.X., Rochon, E.R., Fall, J.L., Paueksakon, P., Yang, H., Alford, C.E., Roman, B.L., Zhang, M.Z., Harris, R., Hukriede, N.A., de Caestecker, M.P.
ID
ZDB-PUB-150626-5
Date
2016
Source
Journal of the American Society of Nephrology : JASN   27(2): 495-508 (Journal)
Registered Authors
Chiba, Takuto, Hukriede, Neil, Roman, Beth
Keywords
acute renal failure, macrophages, renal injury, renal proximal tubule cell, signaling, tubular epithelium
MeSH Terms
  • Acute Kidney Injury/etiology*
  • Animals
  • Macrophages/physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Signal Transduction*
  • Tretinoin/physiology*
PubMed
26109319 Full text @ J. Am. Soc. Nephrol.
Abstract
Retinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.
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