Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction. - Archive ouverte HAL Access content directly
Journal Articles Kidney International Year : 2012

Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction.

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Abstract

Thrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor-β (TGF-β), 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-β. 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-β1 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.
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Dates and versions

inserm-00919132 , version 1 (16-12-2013)

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Naïke Bige, Nasim Shweke, Safa Benhassine, Chantal Jouanneau, Sophie Vandermeersch, et al.. Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction.. Kidney International, 2012, 81 (12), pp.1226-38. ⟨10.1038/ki.2012.21⟩. ⟨inserm-00919132⟩
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