Simultaneous stabilization of actin cytoskeleton in multiple nephron-specific cells protects the kidney from diverse injury

Kamalika Mukherjee, Changkyu Gu, Agnieszka Collins, Marcel Mettlen, Beata Samelko, Mehmet M. Altintas, Yashwanth R. Sudhini, Xuexiang Wang, Richard Bouley, Dennis Brown, Bradley P. Pedro, Susan L. Bane, Vineet Gupta, Paul T. Brinkkoetter, Henning Hagmann, Jochen Reiser, Sanja Sever

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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’s role in modulating stiffness and polarity of renal tubular epithelial cells by crosslinking actin filaments into branched networks. Activation of dynamin’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.

Original languageEnglish (US)
Article number2422
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Simultaneous stabilization of actin cytoskeleton in multiple nephron-specific cells protects the kidney from diverse injury'. Together they form a unique fingerprint.

Cite this