@article{62ab60bcc78645229460195544fdab75,
title = "Simultaneous stabilization of actin cytoskeleton in multiple nephron-specific cells protects the kidney from diverse injury",
abstract = "Chronic kidney diseases and acute kidney injury are mechanistically distinct kidney diseases. While chronic kidney diseases are associated with podocyte injury, acute kidney injury affects renal tubular epithelial cells. Despite these differences, a cardinal feature of both acute and chronic kidney diseases is dysregulated actin cytoskeleton. We have shown that pharmacological activation of GTPase dynamin ameliorates podocyte injury in murine models of chronic kidney diseases by promoting actin polymerization. Here we establish dynamin{\textquoteright}s role in modulating stiffness and polarity of renal tubular epithelial cells by crosslinking actin filaments into branched networks. Activation of dynamin{\textquoteright}s crosslinking capability by a small molecule agonist stabilizes the actomyosin cortex of the apical membrane against injury, which in turn preserves renal function in various murine models of acute kidney injury. Notably, a dynamin agonist simultaneously attenuates podocyte and tubular injury in the genetic murine model of Alport syndrome. Our study provides evidence for the feasibility and highlights the benefits of novel holistic nephron-protective therapies.",
author = "Kamalika Mukherjee and Changkyu Gu and Agnieszka Collins and Marcel Mettlen and Beata Samelko and Altintas, {Mehmet M.} and Sudhini, {Yashwanth R.} and Xuexiang Wang and Richard Bouley and Dennis Brown and Pedro, {Bradley P.} and Bane, {Susan L.} and Vineet Gupta and Brinkkoetter, {Paul T.} and Henning Hagmann and Jochen Reiser and Sanja Sever",
note = "Funding Information: We would like to thank Astrid Schauss and Lisa Wirtz (CECAD Imaging Facility, University of Cologne, Germany) for their advice on AFM measurements and analysis. We would like to thank Benjamin Dellaripa for his technical assistance with cell culture and image quantification. We acknowledge support from the National Institutes of Health (R01 DK093773 and DK087985 to S.S.; R01 DK084195 to V.G. and S.S.; GM73165 to M.M.; CA227747 to S.L.B.). C.G. was supported by Rush University Medical Center. Electron microscopy was performed in the Microscopy Core of the Center for Systems Biology/Program in Membrane Biology, which is partially supported by an Inflammatory Bowel Disease Grant DK043351. P.T.B. and H.H. received funding from the DFG (KFO329, BR-BR 2955/8-1), the Koeln Fortune Program of the University of Cologne. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-30101-4",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}