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.
Citation
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. (2016) Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKI. Journal of the American Society of Nephrology : JASN. 27(2):495-508.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping