【摘 要】
：
Expression of renal EP4 significantly increased in wild type mice after water deprivation, indicating that renal EP4 may participate in water homeostasis.Since global knockout of EP4 in mice induced l
【机 构】
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Department of Physiology and Pathophysiology,Peking University Health Science Center;Beijing,China
【出 处】
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International Conference for Physiological Sciences 2012(201
论文部分内容阅读
Expression of renal EP4 significantly increased in wild type mice after water deprivation, indicating that renal EP4 may participate in water homeostasis.Since global knockout of EP4 in mice induced lethal patent ductus arteriosus during perinatal age, we generated EP4 heterozygotes and conditional EP4 knockout mice in our study.EP4 hegerozygotes exhibited mild polyuria and impaired urine concentrating ability with decreased expression of renal AQP2.Immunohistochemistry showed reduced total expression of AQP2 in the kidney and the downregulated distribution of AQP2 in collecting duct apical membrane in EP4 heterozygotes.In addition, we generated kidney speicific EP4 knockout mice by crossing EP4fo/fox with Ksp-cadherin-Cre mice that also exhibited polyuria and urine concentrating disability.Mouse kidney collecting duct cell line IMCD3 cells were stably transfected with AQP2 plasmid in vitro.Treatment of the cells with either EP4 agonists or adenovirus significantly increased AQP2 expression in plasma membrane by Western blot.Meanwhile, immunofluorescence showed enhanced distribution of AQP2 on plasma membrane, further indicating augmented translocation of AQP2 to plasma membrane with EP4 agonists.Both cAMP-PKA and MAPK pathways were activated with EP4 activation, while inhibition of either of the two pathways blocked the translocation of AQP2 to the plasma membrane.In conclusion, renal EP4 activated AQP2 translocation to plasma membrane through cAMP-PKA and MAPK pathways, which increases water permeability of the collecting duct and thus promotes water reabsorption.
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