Department of Pharmacology, School of Basic Medical Sciences, Peking University, State Key Laboratory of Natural and Biomimetic Drugs, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
Departments of Medicine and Physiology, University of California San Francisco, CA 94143, USA.
Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1231-1241. doi: 10.1016/j.bbadis.2017.03.012. Epub 2017 Mar 23.
Aquaporin-3 (AQP3), a transporter of water, glycerol and HO, is expressed in basolateral membranes of principal cells in kidney collecting duct. Here, we report that AQP3 deletion in mice affects renal function and modulates renal injury. We found collecting duct hyperplasia and cell swelling in kidneys of adult AQP3 null mice. After mild renal ischemia-reperfusion (IR), AQP3 null mice had significantly greater blood urea nitrogen (57mg/dl) and creatinine (136μM) than wild-type mice (35mg/dl and 48μM, respectively), and showed renal morphological changes, including tubular dilatation, erythrocyte diapedesis and collecting duct incompletion. MPO, MDA and SOD following IR in AQP3 null mice were significantly different from that in wild-type mice (1.7U/g vs 0.8U/g, 3.9μM/g vs 2.4μM/g, 6.4U/mg vs 11U/mg, respectively). Following IR, AQP3 deletion inhibited activation of mitogen-activated protein kinase (MAPK) signaling and produced an increase in the ratios of Bax/Bcl-2, cleaved caspase-3/caspase-3 and p-p53/p53. Studies in transfected MDCK cells showed that AQP3 expression attenuated reduced cell viability following hypoxia-reoxygenation, with reduced apoptosis and increased MAPK signaling. Our results support a novel role for AQP3 in modulating renal injury and suggest the mechanisms involved in protection against hypoxic injury.
水通道蛋白 3（AQP3）是水、甘油和 HO 的转运体，在肾脏集合管主细胞的基底外侧膜表达。在这里，我们报告说，AQP3 缺失会影响肾脏功能并调节肾脏损伤。我们发现成年 AQP3 敲除小鼠的集合管增生和细胞肿胀。在轻度肾缺血再灌注（IR）后，AQP3 敲除小鼠的血尿素氮（57mg/dl）和肌酐（136μM）显著高于野生型小鼠（分别为 35mg/dl 和 48μM），并表现出肾脏形态学变化，包括肾小管扩张、红细胞穿出和集合管不完整。AQP3 敲除小鼠的髓过氧化物酶（MPO）、丙二醛（MDA）和超氧化物歧化酶（SOD）在 IR 后与野生型小鼠有显著差异（1.7U/g 比 0.8U/g，3.9μM/g 比 2.4μM/g，6.4U/mg 比 11U/mg）。IR 后，AQP3 缺失抑制丝裂原活化蛋白激酶（MAPK）信号通路的激活，并增加 Bax/Bcl-2、裂解 caspase-3/caspase-3 和 p-p53/p53 的比值。在转染的 MDCK 细胞中的研究表明，AQP3 表达减弱了缺氧再复氧后细胞活力的降低，减少了细胞凋亡并增加了 MAPK 信号通路。我们的研究结果支持 AQP3 在调节肾脏损伤方面的新作用，并提示了其在保护缺氧损伤中的机制。
