| First Author | Nlandu-Khodo S | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 10 | PubMed ID | 32369448 |
| Mgi Jnum | J:330775 | Mgi Id | MGI:6717562 |
| Doi | 10.1172/jci.insight.135454 | Citation | Nlandu-Khodo S, et al. (2020) Tubular beta-catenin and FoxO3 interactions protect in chronic kidney disease. JCI Insight 5(10) |
| abstractText | The Wnt/beta-catenin signaling pathway plays an important role in renal development and is reexpressed in the injured kidney and other organs. beta-Catenin signaling is protective in acute kidney injury (AKI) through actions on the proximal tubule, but the current dogma is that Wnt/beta-catenin signaling promotes fibrosis and development of chronic kidney disease (CKD). As the role of proximal tubular beta-catenin signaling in CKD remains unclear, we genetically stabilized (i.e., activated) beta-catenin specifically in murine proximal tubules. Mice with increased tubular beta-catenin signaling were protected in 2 murine models of AKI to CKD progression. Oxidative stress, a common feature of CKD, reduced the conventional T cell factor/lymphoid enhancer factor-dependent beta-catenin signaling and augmented FoxO3-dependent activity in proximal tubule cells in vitro and in vivo. The protective effect of proximal tubular beta-catenin in renal injury required the presence of FoxO3 in vivo. Furthermore, we identified cystathionine gamma-lyase as a potentially novel transcriptional target of beta-catenin/FoxO3 interactions in the proximal tubule. Thus, our studies overturned the conventional dogma about beta-catenin signaling and CKD by showing a protective effect of proximal tubule beta-catenin in CKD and identified a potentially new transcriptional target of beta-catenin/FoxO3 signaling that has therapeutic potential for CKD. |
