| First Author | Bige N | Year | 2012 |
| Journal | Kidney Int | Volume | 81 |
| Issue | 12 | Pages | 1226-38 |
| PubMed ID | 22418977 | Mgi Jnum | J:198184 |
| Mgi Id | MGI:5495628 | Doi | 10.1038/ki.2012.21 |
| Citation | Bige N, et al. (2012) Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction. Kidney Int 81(12):1226-38 |
| abstractText | Thrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor-beta (TGF-beta), and an anti-angiogenic factor, which may prevent kidney repair. Here we investigated whether TSP-1 is involved in the development of chronic kidney disease using rats with unilateral ureteral obstruction, a well-known model to study renal fibrosis. Obstruction of 10 days duration induced inflammation, tubular cell atrophy, dilation, apoptosis, and proliferation, leading to interstitial fibrosis. TSP-1 expression was increased in parallel to that of collagen III and TGF-beta. Relief of the obstruction at day 10 produced a gradual improvement in renal structure and function, the reappearance of peritubular capillaries, and restoration of renal VEGF content over a 7- to 15-day post-relief period. TSP-1 expression decreased in parallel with that of TGF-beta1 and collagen III. Mice in which the TSP-1 gene was knocked out displayed less inflammation and had better preservation of renal tissue and the peritubular capillary network compared to wild-type mice. Additional studies showed that the inflammatory effect of TSP-1 was mediated, at least in part, by monocyte chemoattractant protein-1 and activation of the Th17 pathway. Thus, TSP-1 is an important profibrotic and inflammatory mediator of renal disease. Blockade of its action may be a treatment against the development of chronic kidney disease. |
