Nucleic acid binding of annexin A2 is regulated through angiotensin II/AT1 signaling in kidneys of hypertensive rats (1088.2)

Abstract

The aim was to identify new targets that regulate gene expression at the post‐transcriptional level in hypertension. Heparin affinity chromatography was applied to enrich putative nucleic acid‐binding proteins from kidneys of 2K1C hypertensive rats. A 0.2mm silver clip was used to induce hypertension (sham: 109±8 mmHg, 2K1C: 146±6 mmHg, P<0.05). We found a 36 kDa protein that showed an increased affinity to the nucleic acid mimetic in the 2K1C model. This factor was identified by LCMSMS and western blotting as Annexin A2 (ANXA2), a RNA‐binding protein known to influence mRNA stability and translation. Immunofluorescence staining revealed widespread distribution of ANXA2 throughout the kidney with high levels in endothelial cells, the cells of the Bowman capsule and in the medullary collecting ducts. Infusion of angiotensin II (AngII) reproduced our findings in the 2K1C animals and the AT1a blocker Losartan abolished the effect on Annexin A2. Strikingly, we observed no change in total Annexin A2 protein levels or localization, suggesting that post‐translational modification modulates Annexin A2 function via ANGII/AT1a signalling. In conclusion, AngII regulates the nucleic acid binding activity of Annexin A2 in the kidneys of rats with hypertension and, thus, may be an important regulator of gene expression in this setting.Grant Funding Source: Supported by Lars Hierta Foundation, Magnus Bergvall Foundation, Swedish Society for Medical Researc