Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney
Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function <i>in vivo</i>. 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...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1253 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tarak Srivastava |
| collection | DOAJ |
| description | Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function <i>in vivo</i>. 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 (<i>p</i> < 0.001 at 4 weeks; <i>p</i> = 0.16 at 12 weeks) and X-gal staining (<i>p</i> = 0.008 at 4 weeks; <i>p</i> = 0.65 at 12 weeks). Immunofluorescence microscopy showed a significant increase in phospho-β-catenin (Ser552, <i>p</i> = 0.005) at 4 weeks but not at 12 weeks (<i>p</i> = 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. |
| first_indexed | 2024-03-10T11:15:47Z |
| format | Article |
| id | doaj.art-139480b8633946dea02847cfd6a4c0e9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:15:47Z |
| publishDate | 2021-05-01 |
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| spelling | doaj.art-139480b8633946dea02847cfd6a4c0e92023-11-21T20:23:45ZengMDPI AGCells2073-44092021-05-01105125310.3390/cells10051253Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary KidneyTarak Srivastava0Daniel P. Heruth1R. Scott Duncan2Mohammad H. Rezaiekhaligh3Robert E. Garola4Lakshmi Priya5Jianping Zhou6Varun C. Boinpelly7Jan Novak8Mohammed Farhan Ali9Trupti Joshi10Uri S. Alon11Yuexu Jiang12Ellen T. McCarthy13Virginia J. Savin14Ram Sharma15Mark L. Johnson16Mukut Sharma17Section of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USAChildren’s Mercy Research Institute, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USASchool of Biological Sciences, University of Missouri at Kansas City, Kansas City, MO 64108, USASection of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USADepartment of Pathology and Laboratory Medicine, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USASection of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USAMidwest Veterans’ Biomedical Research Foundation (MVBRF), Kansas City, MO 64128, USAMidwest Veterans’ Biomedical Research Foundation (MVBRF), Kansas City, MO 64128, USADepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35487, USASection of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USADepartment of Health Management and Informatics, University of Missouri, Columbia, MO 65211, USASection of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO 64108, USADepartment of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211, USADepartment of Internal Medicine, The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, KS 66160, USAKansas City VA Medical Center, Kansas City, MO 64128, USAKansas City VA Medical Center, Kansas City, MO 64128, USADepartment of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri at Kansas City, Kansas City, MO 64108, USAMidwest Veterans’ Biomedical Research Foundation (MVBRF), Kansas City, MO 64128, USAIncreased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function <i>in vivo</i>. 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 (<i>p</i> < 0.001 at 4 weeks; <i>p</i> = 0.16 at 12 weeks) and X-gal staining (<i>p</i> = 0.008 at 4 weeks; <i>p</i> = 0.65 at 12 weeks). Immunofluorescence microscopy showed a significant increase in phospho-β-catenin (Ser552, <i>p</i> = 0.005) at 4 weeks but not at 12 weeks (<i>p</i> = 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.https://www.mdpi.com/2073-4409/10/5/1253podocytesfluid flow shear stressglomerular hemodynamicshyperfiltrationglomerular filtration barrier |
| spellingShingle | 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 Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney Cells podocytes fluid flow shear stress glomerular hemodynamics hyperfiltration glomerular filtration barrier |
| title | Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney |
| title_full | Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney |
| title_fullStr | Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney |
| title_full_unstemmed | Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney |
| title_short | Transcription Factor β-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney |
| title_sort | transcription factor β catenin plays a key role in fluid flow shear stress mediated glomerular injury in solitary kidney |
| topic | podocytes fluid flow shear stress glomerular hemodynamics hyperfiltration glomerular filtration barrier |
| url | https://www.mdpi.com/2073-4409/10/5/1253 |
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