| First Author | Wang S | Year | 2017 |
| Journal | J Cell Mol Med | Volume | 21 |
| Issue | 9 | Pages | 1967-1978 |
| PubMed ID | 28266128 | Mgi Jnum | J:271834 |
| Mgi Id | MGI:6282207 | Doi | 10.1111/jcmm.13117 |
| Citation | Wang S, et al. (2017) Ablation of endothelial prolyl hydroxylase domain protein-2 promotes renal vascular remodelling and fibrosis in mice. J Cell Mol Med 21(9):1967-1978 |
| abstractText | Accumulating evidence demonstrates that hypoxia-inducible factor (HIF-alpha) hydroxylase system has a critical role in vascular remodelling. Using an endothelial-specific prolyl hydroxylase domain protein-2 (PHD2) knockout (PHD2(EC) KO) mouse model, this study investigates the regulatory role of endothelial HIF-alpha hydroxylase system in the development of renal fibrosis. Knockout of PHD2 in EC up-regulated the expression of HIF-1alpha and HIF-2alpha, resulting in a significant decline of renal function as evidenced by elevated levels of serum creatinine. Deletion of PHD2 increased the expression of Notch3 and transforming growth factor (TGF-beta1) in EC, thus further causing glomerular arteriolar remodelling with an increased pericyte and pericyte coverage. This was accompanied by a significant elevation of renal resistive index (RI). Moreover, knockout of PHD2 in EC up-regulated the expression of fibroblast-specific protein-1 (FSP-1) and increased interstitial fibrosis in the kidney. These alterations were strongly associated with up-regulation of Notch3 and TGF-beta1. We concluded that the expression of PHD2 in endothelial cells plays a critical role in renal fibrosis and vascular remodelling in adult mice. Furthermore, these changes were strongly associated with up-regulation of Notch3/TGF-beta1 signalling and excessive pericyte coverage. |
