Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Epublish 4 citations
PubMed: 37698919 DOI: 10.1172/jci.insight.173144
Inhibition of retinoic acid signaling in proximal tubular epithelial cells protects against acute kidney injury.
JCI Insight 8(20)
Authors: Min Yang, Lauren N Lopez, Maya Brewer, Rachel Delgado, Anna Menshikh, Kelly Clouthier, Yuantee Zhu, Thitinee Vanichapol, Haichun Yang, Raymond C Harris, Leslie Gewin, Craig R Brooks, Alan J Davidson, Mark de Caestecker
Affiliations
- Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- Department of Molecular Medicine & Pathology, The University of Auckland, Auckland, New Zealand.
- Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- Washington University in St. Louis School of Medicine and the St. Louis Veterans Affairs Hospital, St. Louis, Missouri, USA.
Abstract
Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development but, in the adult kidney, is restricted to occasional collecting duct epithelial cells. We now show that there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI) and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protected against experimental AKI but was unexpectedly associated with increased expression of the PTEC injury marker Kim1. However, the protective effects of inhibiting PTEC RAR signaling were associated with increased Kim1-dependent apoptotic cell clearance, or efferocytosis, and this was associated with dedifferentiation, proliferation, and metabolic reprogramming of PTECs. These data demonstrate the functional role that reactivation of RAR signaling plays in regulating PTEC differentiation and function in human and experimental AKI.
MeSH
Epithelial Cells, Biomedical Research, Tretinoin, Acute Kidney Injury
Cited by
- Permanent defects in renal medullary structure and function after reversal of urinary obstruction. JCI Insight, 2025
- Resazurin dye is an in vivo sensor of kidney tubular function. Kidney Int, 2025
- The role of inflammatory response and metabolic reprogramming in sepsis-associated acute kidney injury: mechanistic insights and therapeutic potential. Front Immunol, 2024