ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: FR-PO930

Regulation of Cytoskeletal Assembly by YAP (Yes-Associated-Protein) Mediates Podocyte Repair During the Response to Glomerular Injury

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology


  • Huynh Cong, Evelyne, Boston Children's Hospital, Boston, Massachusetts, United States
  • Weins, Astrid, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Schumacher, Valerie A., Boston Children's Hospital, Boston, Massachusetts, United States
  • Taglienti, Mary E., Boston Children's Hospital, Boston, Massachusetts, United States
  • Kreidberg, Jordan A., Boston Children's Hospital, Boston, Massachusetts, United States

The HIPPO signaling pathway regulates the YAP/TAZ-Tead transcription factor complex involved in cell growth to determine organ size. Published studies have suggested that YAP is required for podocyte survival.


Yap was conditionally inactivated in podocytes of adult mice using an inducible Cre recombinase. In vitro, immortalized differentiated mouse podocytes were treated with Yap siRNAs. Podocyte injury was induced by treatment with adriamycin or trypsinization, in vivo or in vitro respectively. Electron microscopy, histology, molecular and cellular biology studies were conducted to characterize the phenotype of either Yap knockout mice or Yap knockdown cells.


Electron microscopy analysis eight weeks after Yap inactivation in mouse revealed that Yap knockout led to mild foot process effacement. However, there was no evidence of proteinuria or glomerulosclerosis in Yap knockout mice, suggesting that there may be a redundant function of TAZ in uninjured podocytes. Treatment of Yap mutant mice with Adriamycin led to microalbuminuria and an increased frequency of histological lesions resembling Focal Segmental Glomerulosclerosis.
Yap knockdown in immortalized differentiated mouse podocytes led to a reduction in focal adhesion area per cell and decreased area per cell. Yap siRNA treatment also led to a dramatic inability to spread and to organize actin stress fibers after trypsinization and reseeding. Consistent with the inability to spread, levels of pY397 FAK and phospho-cofilin, a downstream target of RhoA GTPase, were reduced in Yap knockdown podocytes. Yap knockdown also led to decreased inactivation of Rac1, a member of the Rho GTPAse family.


Our studies demonstrate that YAP has a crucial role in the assembly of the actin cytoskeleton during recovery from injury, affecting the polymerization of actin mediated by Rho family GTPases. In vivo, YAP appears to have a greater role in recovery from injury than in maintaining the cytoskeleton in uninjured podocytes.


  • NIDDK Support