Stress-responsive gene TauT and acute kidney injury

Journal of Biomedical Science

Review

Russell W Chesney¹  Xiaobin Han¹ 

[1] Department of Pediatrics, University of Tennessee Health Science Center, and the Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee, USA;

关键词: Taurine;    Acute Kidney Injury;    Taurine Transport;    Outer Stripe;    Renal Proximal Tubular Cell;   

DOI  :  10.1186/1423-0127-17-S1-S28

来源: Springer

【 摘 要 】

BackgroundCisplatin is a commonly used chemotherapeutic agent that has a major limitation because of its nephrotoxicity. We have demonstrated that cisplatin down-regulates the expression of the taurine transporter gene (TauT) in renal cells and that forced overexpression of TauT protects against cisplatin-induced apoptosis in renal cells in vitro and in vivo. In the present study, we have investigated how TauT is regulated by p53 and c-Jun and its role during acute kidney injury (AKI).MethodsRegulation of TauT by p53 and c-Jun was determined by reporter gene assay, DNA binding, Western blot analysis, and immunohistochemistry.ResultsTauT was down-regulated by p53 and up-regulated by c-Jun. Two potential binding sites for c-Jun were identified in the promoter region of TauT. Inhibition of c-Jun N-terminal kinase (JNK) enhanced TauT promoter activity. Overexpression of TauT protects against cisplatin-induced kidney injury in a TauT transgenic mouse model.ConclusionsOur findings suggest that TauT plays a critical role in renal function. Expression of TauT is negatively regulated by p53 and positively regulated by c-Jun, which is mediated by the JNK signaling pathway. The outcome level of TauT may determine the fate of renal cells during stress-induced AKI.

【 授权许可】

CC BY   
© Han and Chesney; licensee BioMed Central Ltd. 2010