α‐actinin 4 Knockdown Reduced Vasopressin‐Induced Aquaporin‐2 Expression in the Kidney Collecting Duct Cells

Abstract

Vasopressin is a pituitary peptide hormone that regulates aquaporin‐2 (AQP2) gene expression in the kidney collecting duct principal cells. Dysregulation of vasopressin‐regulated AQP2 gene expression is associated with many water balance disorders. Previously in the collecting duct cell model (mpkCCD), we identified α actinin 4, a cytoskeletal actin‐binding protein that was reported to translocate into the nucleus and acts as a transcriptional co‐activator. Here, we found that short hairpin RNA (shRNA)‐mediated α actinin 4 knockdown in the mpkCCD cells reduced vasopressin‐induced AQP2 mRNA and protein levels, suggesting a role of α actinin 4 in vasopressin‐induced AQP2 gene expression. However, vasopressin did not induce nuclear translocation of α actinin 4, suggesting a different model of α actinin 4 action. α actinin 4 was reported as a transcriptional co‐activator of the glucocorticoid receptor whose agonist dexamethasone was shown to enhance vasopressin‐induced AQP2 gene expression in the mpkCCD cells in a dose‐ and time‐dependent manner. We thus tested whether α actinin 4 interacts with glucocorticoid receptor to enhance vasopressin‐induced AQP2 gene expression. In support of our hypothesis, shRNA‐mediated glucocorticoid receptor knockdown almost blunted vasopressin‐induced AQP2 mRNA and protein expression. Our results are consistent with a role of α actinin 4 in vasopressin‐induced AQP2 gene expression involving glucocorticoid receptor.Support or Funding InformationThis work was supported by Ministry of Science and Technology, Taiwan to MJY (MOST104‐2320‐B002‐064‐MY3)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.