| First Author | Hou Q | Year | 2021 |
| Journal | Front Cell Dev Biol | Volume | 9 |
| Pages | 781792 | PubMed ID | 35004680 |
| Mgi Jnum | J:317698 | Mgi Id | MGI:6852996 |
| Doi | 10.3389/fcell.2021.781792 | Citation | Hou Q, et al. (2021) Nuclear Receptor Interacting Protein-2 Mediates the Stabilization and Activation of beta-Catenin During Podocyte Injury. Front Cell Dev Biol 9:781792 |
| abstractText | Objective: Activation of beta-catenin causes podocyte injury and proteinuria, but how beta-catenin signalling is regulated during podocyte injury remains elusive. Nuclear receptor interacting protein 2 (NRIP2) modulates the Wnt pathway in colorectal cancer-initiating cells, but the role of NRIP2 in podocyte injury has not yet been investigated. We aimed to examine the interaction between NRIP2 and beta-catenin signalling. Materials and Methods: Knockdown or overexpression of NRIP2 and beta-catenin and chemical treatments were performed in cultured human podocytes. Immunoprecipitation, immunoblotting and immunofluorescence assays were used to assess protein interactions and expression. Data from the GEO dataset and kidney tissues from patients with focal segmental glomerulosclerosis (FSGS) and surgical nephrectomy were examined. An adriamycin (ADR) nephropathy model was established in NRIP2 knockout mice. Results: NRIP2 knockdown accelerated beta-catenin degradation, which was reversed by MG132; specifically, NRIP2 bound beta-catenin and stabilized it to prevent its degradation through the ubiquitin proteasomal pathway. Overexpression of NRIP2 led to beta-catenin activation and Snail1 induction, and these effects were attenuated by beta-catenin knockdown. NRIP2 knockdown blocked ADR-stimulated beta-catenin activation. In ADR mice, genetic knockout of Nrip2 ameliorated podocyte injury and loss, glomerulosclerosis, and proteinuria by inhibiting beta-catenin activation. Moreover, NRIP2 was significantly upregulated in podocytes of FSGS patients and colocalized with nuclear beta-catenin. Conclusion: These results established NRIP2 as a stabilizer of beta-catenin activation through the ubiquitin proteasomal pathway in podocyte injury. |
