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Article

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

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Section of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA
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Midwest Veterans’ Biomedical Research Foundation (MVBRF), Kansas City, MO 64128, USA
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Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri at Kansas City, Kansas City, MO 64108, USA
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Children’s Mercy Research Institute, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA
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School of Biological Sciences, University of Missouri at Kansas City, Kansas City, MO 64108, USA
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Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USA
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Kansas City VA Medical Center, Kansas City, MO 64128, USA
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Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35487, USA
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Department of Health Management and Informatics, University of Missouri, Columbia, MO 65211, USA
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Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211, USA
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Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA
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MU Data Science and Informatics Institute, University of Missouri, Columbia, MO 65211, USA
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Department of Internal Medicine, The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USA
*
Author to whom correspondence should be addressed.
Academic Editor: James Albert McCubrey
Cells 2021, 10(5), 1253; https://doi.org/10.3390/cells10051253
Received: 21 April 2021 / Revised: 6 May 2021 / Accepted: 14 May 2021 / Published: 19 May 2021
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 < 0.001 at 4 weeks; 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. View Full-Text
Keywords: podocytes; fluid flow shear stress; glomerular hemodynamics; hyperfiltration; glomerular filtration barrier podocytes; fluid flow shear stress; glomerular hemodynamics; hyperfiltration; glomerular filtration barrier
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MDPI and ACS Style

Srivastava, T.; Heruth, D.P.; Duncan, R.S.; Rezaiekhaligh, M.H.; Garola, R.E.; Priya, L.; Zhou, J.; Boinpelly, V.C.; Novak, J.; Ali, M.F.; Joshi, T.; Alon, U.S.; Jiang, Y.; McCarthy, E.T.; Savin, V.J.; Sharma, R.; Johnson, M.L.; Sharma, M. Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney. Cells 2021, 10, 1253. https://doi.org/10.3390/cells10051253

AMA Style

Srivastava T, Heruth DP, Duncan RS, Rezaiekhaligh MH, Garola RE, Priya L, Zhou J, Boinpelly VC, Novak J, Ali MF, Joshi T, Alon US, Jiang Y, McCarthy ET, Savin VJ, Sharma R, Johnson ML, Sharma M. Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney. Cells. 2021; 10(5):1253. https://doi.org/10.3390/cells10051253

Chicago/Turabian Style

Srivastava, Tarak, 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, and Mukut Sharma. 2021. "Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney" Cells 10, no. 5: 1253. https://doi.org/10.3390/cells10051253

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