Fang Yi

Effect of Body Mass Index on Acute Kidney Injury After Cardiac Surgery

Background: Trichorhinophalangeal 1 (Trps1) is essential for epithelial cell morphogenesis during kidney development. But its role in acute kidney injury induced by ischemia/reperfusion (I/R) remains unclear. Methods: The rat models of renal I/R injury were established by clamping bilateral renal arteries for 45 min (moderate I/R) or for 60 min (severe I/ R) and reperfusion. The renal tubule epithelial NRK-52E cells were cultured under hypoxic conditions for 4 h to induce hypoxic injury, followed by reoxygenation (H/R). Trps1-siRNA or Trps1-overexpression vectors were transferred by ultrasound-microbubble-mediated gene transfer system. The changes of gene expression were analyzed by real-time PCR and Western blotting. Promoter activities of transcription factors were estimated by dual luciferase reporter gene assay. Results: Knockdown of Trps1 significantly delayed renal repair in moderate I/R model as evidenced by higher serum creatinine levels and more severe morphological injury compared with wild-type rat (P < 0.05), whereas overexpression of Trps1 significantly accelerated renal repair after severe I/R injury. Knockdown of Trps1 decreased the proportion of IdU positive cells in rat kidneys with I/R injury and the level of PCNA in NRK-52E cells after H/R, and vice versa. Furthermore, mRNA level of Notch2 was decreased by 58% and the protein levels of Notch2 and its downstream effector molecule Hes1 were decreased by about 43e67% in Trps1-knockdown rat at 3 day after reperfusion. The dual luciferase analysis demonstrated that Trps1 directly activated Notch2 transcription. And knockdown of Notch2 significantly inhibited Trps1-induced tubular cells proliferation in vitro. Conclusion: Trps1 regulates tubular cells proliferation through Notch2 and promotes kidney repair after I/R injury. Trps1 may serve as a potential therapeutic target for renal repair following I/R injury.