Cells (May 2021)

Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney

  • Tarak Srivastava,
  • Daniel P. Heruth,
  • R. Scott Duncan,
  • Mohammad H. Rezaiekhaligh,
  • Robert E. Garola,
  • Lakshmi Priya,
  • Jianping Zhou,
  • Varun C. Boinpelly,
  • Jan Novak,
  • Mohammed Farhan Ali,
  • Trupti Joshi,
  • Uri S. Alon,
  • Yuexu Jiang,
  • Ellen T. McCarthy,
  • Virginia J. Savin,
  • Ram Sharma,
  • Mark L. Johnson,
  • Mukut Sharma

DOI
https://doi.org/10.3390/cells10051253
Journal volume & issue
Vol. 10, no. 5
p. 1253

Abstract

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Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3β-β-catenin signaling. The present study was undertaken to confirm (i) the activation of β-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL mice with the β-galactosidase reporter gene for β-catenin activation, (ii) β-catenin translocation in FFSS-treated mouse podocytes, and (iii) β-catenin signaling using publicly available data from UNX mice. The UNX of TOPGAL mice resulted in glomerular hypertrophy and increased the mesangial matrix consistent with hemodynamic adaptation. Uninephrectomized TOPGAL mice showed an increased β-galactosidase expression at 4 weeks but not at 12 weeks, as assessed using immunofluorescence microscopy (p p = 0.16 at 12 weeks) and X-gal staining (p = 0.008 at 4 weeks; p = 0.65 at 12 weeks). Immunofluorescence microscopy showed a significant increase in phospho-β-catenin (Ser552, p = 0.005) at 4 weeks but not at 12 weeks (p = 0.935) following UNX, and the levels of phospho-β-catenin (Ser675) did not change. In vitro FFSS caused a sustained increase in the nuclear translocation of phospho-β-catenin (Ser552) but not phospho-β-catenin (Ser675) in podocytes. The bioinformatic analysis of the GEO dataset, #GSE53996, also identified β-catenin as a key upstream regulator. We conclude that transcription factor β-catenin mediates FFSS-induced podocyte (glomerular) injury in solitary kidney.

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