| First Author | Chai Z | Year | 2013 |
| Journal | J Am Soc Nephrol | Volume | 24 |
| Issue | 11 | Pages | 1782-92 |
| PubMed ID | 23929772 | Mgi Jnum | J:264730 |
| Mgi Id | MGI:6198034 | Doi | 10.1681/ASN.2013010060 |
| Citation | Chai Z, et al. (2013) Genetic deletion of cell division autoantigen 1 retards diabetes-associated renal injury. J Am Soc Nephrol 24(11):1782-92 |
| abstractText | Cell division autoantigen 1 (CDA1) enhances TGF-beta 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-beta1, TGF-beta 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-beta1 receptors in the kidney, resulting in a functionally attenuated response to exogenous TGF-beta, including reduced levels of phosphorylated Smad3 and ERK1/2, in primary kidney cells from CDA1 knockout animals. Taken together, these data suggest that CDA1 deletion reduces but does not block renal TGF-beta signaling. Because direct antagonism of TGF-beta or its receptors has unwanted effects, CDA1 may be a potential therapeutic target for retarding DN and perhaps, other kidney diseases associated with TGF-beta-mediated fibrogenesis. |
