| First Author | Dang Y | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 3 | Pages | e89835 |
| PubMed ID | 24595031 | Mgi Jnum | J:214699 |
| Mgi Id | MGI:5603712 | Doi | 10.1371/journal.pone.0089835 |
| Citation | Dang Y, et al. (2014) Gpr48 deficiency induces polycystic kidney lesions and renal fibrosis in mice by activating Wnt signal pathway. PLoS One 9(3):e89835 |
| abstractText | G protein-coupled receptor 48 (Gpr48/Lgr4) is essential to regulate the development of multiple tissues in mice. The notion that Gpr48 functions in renal development prompted us to investigate the relation between Gpr48 and renal diseases. Using a Gpr48 knockout mice model, we observed that 66.7% Gpr48 null mice developed polycystic lesions in the kidney, while no cysts were observed in the kidneys of wild-type mice. Polycystic kidney disease 1 (PKD1) and PKD2 expressions were also markedly decreased in the Gpr48 knockout mice. Abnormal expressions of exra-cellular matrix protein lead to the progression of polycystic kidney disease and the formation of renal fibrosis in the Gpr48 null mice. The expressions of several Wnt molecules and its receptors were increased and marked beta-catenin nuclear accumulation was observed in the Gpr48 null mice. The inhibitors of Wnt/beta-catenin signal pathway such as GSK3beta and axin2 were loss of function. The Wnt/PCP signaling pathway is also activated in Gpr48 null mice. However, TGF-beta expression and phosphorylated Smad2/3 levels were not altered. Collectively, our results showed that Gpr48 null mice are at a greater risk of suffering from polycystic lesions and renal fibrosis. Moreover, the formation of polycystic lesions and renal fibrosis induced by Gpr48 deficiency involves the activation of Wnt signaling pathway but not the TGF-beta/Smad pathway. |
