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Title page for ETD etd-05272015-145940

Type of Document Dissertation
Author Chiba, Takuto
Author's Email Address takuto.chiba@vanderbilt.edu
URN etd-05272015-145940
Title The Role of Retinoic Acid Signaling in Acute Kidney Injury
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
David M. Bader Committee Chair
Guoqiang Gu Committee Member
H. Scott Baldwin Committee Member
Reymond C. Harris Committee Member
  • inflammation
  • acute kidney injury
  • retinoic acid signaling
  • fibrosis
  • proximal tubular epithelial cell
  • macrophage
Date of Defense 2015-05-11
Availability unrestricted
Retinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of acute kidney injury (AKI), but little is known about whether and how this pathway is normally regulated, and what role it plays 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 are mediated through a novel mechanism by which RA signaling coordinates the dynamic equilibrium of pro-inflammatory M1 spectrum vs. alternatively activated M2 spectrum macrophages. According to this model, direct repression of pro-inflammatory macrophages by locally synthesized RA reduces macrophage-dependent injury post-AKI, while locally synthesized RA activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Since RA signaling plays 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 injury and plays an important role in reducing injury and enhancing repair after AKI.
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