@article{1e20bfe7018e488f8643e89366094cc7,
title = "Dynamin-related protein 1 deficiency promotes recovery from AKI",
abstract = "The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective b-hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.",
author = "Perry, {Heather M.} and Liping Huang and Wilson, {Rebecca J.} and Amandeep Bajwa and Hiromi Sesaki and Zhen Yan and Rosin, {Diane L.} and Kashatus, {David F.} and Okusa, {Mark D.}",
note = "Funding Information: Research conducted for this publication was supported by National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health awards F32DK108563 (to H.M.P.), T32DK72922 (to H.M.P.), American Society of Nephrology Ben Lipps Fellowship Program (to H.M.P.), DK091444 (to A.B.), DK107941 (to A.B.), R01 062324 (to M.D.O.), and R01 085259 (to M.D.O.). The stereology data described here were gathered on an MBF Bioscience and Zeiss microscope system for stereology and tissue morphology funded by National Institutes of Health grant 1S10RR026799-01 (to M.D.O.). Electron micrographs were obtained by using a JEOL Model JEM-1230 Transmission Electron Microscope funded by National Institutes of Health grant 1S10RR021017-01. Funding Information: We thank the University of Virginia Research Histology Core for their assistance in preparation of histology slides. We would also like to thank Dr. Benjamin Humphreys (Washington University) for providing the iSLC34a1CreERT2 mice. Research conducted for this publication was supported by National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health awards F32DK108563 (to H.M.P.), T32DK72922 (to H.M.P.), American Society of Nephrology Ben Lipps Fellowship Program (to H.M.P.), DK091444 (to A.B.), DK107941 (to A.B.), R01 062324 (to M.D.O.), and R01 085259 (to M.D.O.). The stereology data described here were gathered on an MBF Bioscience and Zeiss microscope system for stereology and tissue morphology funded by National Institutes of Health grant 1S10RR026799-01 (to M.D.O.). Electron micrographs were obtained by using a JEOL Model JEM-1230 Transmission Electron Microscope funded by National Institutes of Health grant 1S10RR021017-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: Copyright {\textcopyright} 2018 by the American Society of Nephrology.",
year = "2018",
month = jan,
doi = "10.1681/ASN.2017060659",
language = "English (US)",
volume = "29",
pages = "194--206",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "1",
}