| First Author | Hsu YC | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 30575 | PubMed ID | 27460630 |
| Mgi Jnum | J:295340 | Mgi Id | MGI:6221049 |
| Doi | 10.1038/srep30575 | Citation | Hsu YC, et al. (2016) Protective effects of miR-29a on diabetic glomerular dysfunction by modulation of DKK1/Wnt/beta-catenin signaling. Sci Rep 6:30575 |
| abstractText | Dysregulation of specific microRNAs or Wnt/beta-catenin signaling pathway is critically implicated in the pathogenesis of various renal diseases. However, the relationship between microRNAs and Wnt/beta-catenin signaling in diabetes-induced glomerular sclerosis remains unknown. Here, we found that decreased miR-29a expression and attenuated Wnt/beta-catenin signaling were concomitantly detected in glomeruli of streptozotocin-induced diabetic mice. Gain of miR-29a function in diabetic mice substantially increased the expression of beta-catenin and blocked the expressions of profibrotic gene markers, including DKK1 (a Wnt antagonist), TGF-beta1 and fibronectin, in glomerular mesangium. Moreover, in the normal mice treated with miR-29a inhibitor, renal fibrosis was induced with an attenuated Wnt/beta-catenin signaling activity. Consistently, the constructed miR-29a transgenic mice that supported sustained Wnt/beta-catenin signaling had the ability to block the expressions of profibrotic genes after induction of diabetes. We also demonstrated that miR-29a acts as a positive regulator of Wnt/beta-catenin signaling in cultured mesangial cells and functions to protect cell apoptosis and fibrosis. Importantly, we showed that activation of Wnt/beta-catenin signaling in cultured mesangial cells by transfecting the beta-catenin (Delta45) mutant or by a GSK-3beta inhibitor reversely upregulated miR29a. Our findings suggest that the reciprocal relationship between miR-29a and DKK1/Wnt/beta-catenin signaling may play an important part in protecting renal fibrogenesis. |
