2. Academic Validation
  3. The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus

The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus

  • Nat Commun. 2025 Apr 8;16(1):3322. doi: 10.1038/s41467-025-58567-y.
Evelyne Huynh-Cong 1 2 3,  Victoria Driscoll 4,  Sandrine Ettou 1 2,  Keith Keller 5 6,  Amha Atakilit 7,  Mary E Taglienti 1,  Saurabh Kumar 1 8,  Astrid Weins 5,  Valerie A Schumacher 9 10 11 12 13,  Jordan A Kreidberg 14 15 16 17 18 19
Affiliations

Affiliations

  • 1 Department of Urology, Boston Children's Hospital, Boston, MA, USA.
  • 2 Department of Surgery, Harvard Medical School, Boston, MA, USA.
  • 3 for EHC: Evotec, Gottinggen, Germany.
  • 4 Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • 5 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • 6 Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • 7 Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • 8 for SK: University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.
  • 9 Department of Urology, Boston Children's Hospital, Boston, MA, USA. VSchumac@bidmc.harvard.edu.
  • 10 Department of Surgery, Harvard Medical School, Boston, MA, USA. VSchumac@bidmc.harvard.edu.
  • 11 Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, USA. VSchumac@bidmc.harvard.edu.
  • 12 Department of Medicine, Harvard Medical School, Boston, MA, USA. VSchumac@bidmc.harvard.edu.
  • 13 for VAS and JAK: Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA. VSchumac@bidmc.harvard.edu.
  • 14 Department of Urology, Boston Children's Hospital, Boston, MA, USA. Jkreidbe@bidmc.harvard.edu.
  • 15 Department of Surgery, Harvard Medical School, Boston, MA, USA. Jkreidbe@bidmc.harvard.edu.
  • 16 Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Jkreidbe@bidmc.harvard.edu.
  • 17 Department of Medicine, Harvard Medical School, Boston, MA, USA. Jkreidbe@bidmc.harvard.edu.
  • 18 Harvard Stem Cell Institute, Cambridge, MA, USA. Jkreidbe@bidmc.harvard.edu.
  • 19 for VAS and JAK: Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA. Jkreidbe@bidmc.harvard.edu.
PMID: 40199893 DOI: 10.1038/s41467-025-58567-y
Abstract

The kidney glomerulus is a filtration barrier in which capillary loop architecture depends on epithelial-stromal interactions between podocytes and mesangial cells. Podocytes are terminally differentiated cells within the glomerulus that express YAP and TAZ. Here we test the hypotheses that YAP and TAZ are required in podocytes to maintain capillary loop architecture and that shifts in the Integrin repertoire during podocyte injury affect transcriptional activity of YAP and TAZ. Loss of YAP in podocytes of adult mice renders them more sensitive to injury, whereas loss of both YAP and TAZ in podocytes rapidly compromises the filtration barrier. α3β1 and αvβ5 are two prominent integrins on murine podocytes. Podocyte injury or loss of α3β1 leads to increased abundance of αvβ5 and nuclear localization of YAP. In vitro, blockade of αvβ5 decreases nuclear YAP. Increased αv integrins are found in human kidney disease. Thus, our studies demonstrate the crucial regulatory interplay between cell adhesion and transcriptional regulation as an important determinant of human disease.

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