Genetic deletion of cell division autoantigen 1 retards diabetes-associated renal injury (original) (raw)

Journal of the American Society of Nephrology : JASN, 2013

Abstract

Cell division autoantigen 1 (CDA1) enhances TGF-β signaling in renal and vascular cells, and renal expression of CDA1 is elevated in animal models of diabetes. In this study, we investigated the genetic deletion of Tspyl2, the gene encoding CDA1, in C57BL6 and ApoE knockout mice. The increased renal expression of TGF-β1, TGF-β type I and II receptors, and phosphorylated Smad3 associated with diabetes in wild-type mice was attenuated in diabetic CDA1 knockout mice. Notably, CDA1 deletion significantly reduced diabetes-associated renal matrix accumulation and immunohistochemical staining for collagens III and IV and attenuated glomerular and tubulointerstitial injury indices, despite the presence of persistent hyperglycemia, polyuria, renal hypertrophy, and hyperfiltration. Furthermore, CDA1 deletion reduced gene expression of TGF-β1 receptors in the kidney, resulting in a functionally attenuated response to exogenous TGF-β, including reduced levels of phosphorylated Smad3 and ERK1/2,...

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