Abstract 51: Periostin: a Novel Mediator of Renal Disease
Introduction: Chronic Kidney Disease (CKD) is characterized by progressive decrease in renal function related to a progressive accumulation of fibrosis. The lack of efficient treatment makes urgent the finding of novel targets for therapy. In previous studies we have shown that periostin, a protein normally involved in the regulation of osteoblasts’ differentiation, is abnormally and highly expressed in several models of CKD, and is inversely correlated with the decline of renal function.
Objectives: To investigate whether periostin, in addition to be a biomarker of CKD, is also involved in mechanisms leading to the development of renal disease.
Methods: Unilateral ureteral obstruction (UUO) was applied in periostin knock-out/beta-galactosidase knock-in and wild type littermate mice. The expression of periostin was evaluated by quantitative RT-PCR, Western Blot and immunocytochemistry in the wt mice. The localization of periostin synthesis within renal cortex was determined by the reporter gene LacZ in the KO mice. The expression of other genes, well-known for their pro-fibrotic and inflammatory action was also studied by RT-PCR, WB and IHC.
Results: Following UUO, periostin expression (mRNA and protein) was several-fold induced in the tubular interstitium of wt mice. Periostin synthesis occurred within the collecting duct in the beginning of the disease, and then around altered/dilated tubules as the disease progressed. Periostin KO mice were protected compared to wild type as they displayed less tubular dilation and fibrosis (p<0.01), and the activation of genes associated to renal disease like collagen I, TGFbeta, vimentin and MCP-1 was blunted (p<0.01). In addition, periostin KO mice displayed increased rates of proliferation of tubular cells ( p<0.001), and preserved E-cadherin expression.
Conclusion: Induction of periostin expression is an early and important event of CKD. Genetic inhibition of periostin expression leads to a better preservation of the renal tissue in the UUO model. These results suggest that blocking periostin can be a novel and promising target against the development of CKD
- © 2012 by American Heart Association, Inc.