• Mi Liu, Ying Sun, Man Xu, Xiaowen Yu, Yue Zhang, Songming Huang, Guixia Ding, Aihua Zhang, and Zhanjun Jia.
• Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University , Nanjing , China.
• Am. J. Physiol. Renal Physiol. 2018 Apr 1; 314 (4): F658-F666.

AbstractDownregulation of aquaporins (AQPs) in obstructive kidney disease has been well demonstrated with elusive mechanisms. Our previous study indicated that mitochondrial dysfunction played a crucial role in this process. However, it is still uncertain how mitochondrial dysfunction affected the AQPs in obstructive kidney disease. This study investigated the role of mitochondria-derived oxidative stress in mediating obstruction-induced downregulation of AQPs. After unilateral ureteral obstruction for 7 days, renal superoxide dismutase 2 (SOD2; mitochondria-specific SOD) was reduced by 85%. Meanwhile, AQP1, AQP2, AQP3, and AQP4 were remarkably downregulated as determined by Western blotting and/or quantitative real-time PCR. Administration of the SOD2 mimic manganese (III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) significantly attenuated AQP2 downregulation in line with complete blockade of thiobarbituric acid-reactive substances elevation, whereas the reduction of AQP1, AQP3, and AQP4 was not affected. The cyclooxygenase (COX)-2/prostaglandin (PG) E2 pathway has been well documented as a contributor of AQP reduction in obstructed kidney; thus, we detected the levels of COX-1/2 and microsomal prostaglandin E synthase 1 (mPGES-1) in kidney and PGE2 secretion in urine. Significantly, MnTBAP partially suppressed the elevation of COX-2, mPGES-1, and PGE2. Moreover, a marked decrease of V2 receptor was significantly restored after MnTBAP treatment. However, the fibrotic response and renal tubular damage were unaffected by MnTBAP in obstructed kidneys. Collectively, these findings suggested an important role of mitochondrial oxidative stress in mediating AQP2 downregulation in obstructed kidney, possibly via modulating the COX-2/mPGES-1/PGE2/V2 receptor pathway.

61 keywords...

hide…