| First Author | Srivastava T | Year | 2021 |
| Journal | Cells | Volume | 10 |
| Issue | 5 | PubMed ID | 34069476 |
| Mgi Jnum | J:314503 | Mgi Id | MGI:6813200 |
| Doi | 10.3390/cells10051253 | Citation | Srivastava T, et al. (2021) Transcription Factor beta-Catenin Plays a Key Role in Fluid Flow Shear Stress-Mediated Glomerular Injury in Solitary Kidney. Cells 10(5) |
| abstractText | Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3beta-beta-catenin signaling. The present study was undertaken to confirm (i) the activation of beta-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL mice with the beta-galactosidase reporter gene for beta-catenin activation, (ii) beta-catenin translocation in FFSS-treated mouse podocytes, and (iii) beta-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 beta-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-beta-catenin (Ser552, p = 0.005) at 4 weeks but not at 12 weeks (p = 0.935) following UNX, and the levels of phospho-beta-catenin (Ser675) did not change. In vitro FFSS caused a sustained increase in the nuclear translocation of phospho-beta-catenin (Ser552) but not phospho-beta-catenin (Ser675) in podocytes. The bioinformatic analysis of the GEO dataset, #GSE53996, also identified beta-catenin as a key upstream regulator. We conclude that transcription factor beta-catenin mediates FFSS-induced podocyte (glomerular) injury in solitary kidney. |
