| First Author | Cui W | Year | 2014 |
| Journal | Am J Physiol Renal Physiol | Volume | 306 |
| Issue | 9 | Pages | F996-1007 |
| PubMed ID | 24573388 | Mgi Jnum | J:210528 |
| Mgi Id | MGI:5571410 | Doi | 10.1152/ajprenal.00657.2013 |
| Citation | Cui W, et al. (2014) Increasing cGMP-dependent protein kinase activity attenuates unilateral ureteral obstruction-induced renal fibrosis. Am J Physiol Renal Physiol 306(9):F996-1007 |
| abstractText | Our previous studies support the protective effect of cGMP and cGMP-dependent protein kinase I (PKG-I) pathway on the development of renal fibrosis. Therefore, in the present studies, we determined whether pharmacologically or genetically increased PKG activity attenuates renal fibrosis in a unilateral ureteral obstruction (UUO) model and also examined the mechanisms involved. To increase PKG activity, we used the phosphodiesterase 5 inhibitor sildenafil and PKG transgenic mice. UUO model was induced in wild-type or PKG-I transgenic mice by ligating the left lateral ureteral and the renal fibrosis was observed after 14 days of ligation. Sildenafil was administered into wild-type UUO mice for 14 days. In vitro, macrophage and proximal tubular cell function was also analyzed. We found that sildenafil treatment or PKG transgenic mice had significantly reduced UUO-induced renal fibrosis, which was associated with reduced TGF-beta signaling and reduced macrophage infiltration into kidney interstitial. In vitro data further demonstrated that both macrophages and proximal tubular cells were important sources of UUO-induced renal TGF-beta levels. The interaction between macrophages and tubular cells contributes to TGF-beta-induced renal fibrosis. Taken together, these data suggest that increasing PKG activity ameliorates renal fibrosis in part through regulation of macrophage and tubular cell function, leading to reduced TGF-beta-induced fibrosis. |
