NFAT5 regulates renal gene expression in response to Angiotensin II through Annexin-A2-mediated post-transcriptional regulation in hypertensive rats.
Authors of this article are:
Fähling M, Paliege A, Jönsson S, Becirovic-Agic M, Melville JM, Skogstrand T, Hultström M.
A summary of the article is shown below:
The aim was to identify new targets that regulate gene expression at the post-transcriptional level in Angiotensin II (ANGII)-mediated hypertension. Heparin affinity chromatography was used to enrich nucleic acid-binding proteins from kidneys of two-kidney, one-clip (2K1C) hypertensive Wistar rats. The experiment was repeated with 14 days ANGII infusion using Alzet osmotic mini pumps, with or without ANGII receptor AT1a inhibition using Losartan in the drinking water. Mean arterial pressure increased after 2K1C or ANGII infusion and was inhibited with Losartan.Heparin affinity chromatography and mass spectrometry were used to identify Annexin-A2 (ANXA2) as having differential nucleic acid binding activity.Total Annexin-A2 protein expression was unchanged, while nucleic acid binding activity was increased in both kidneys of 2K1C and after ANGII infusion through AT1a stimulation.Co-staining of Annexin-A2 with Alpha-SMA and AQP2 showed prominent expression in the endothelium of larger arteries and the cells of the inner medullary collecting duct (IMCD). The NFAT transcription factor was identified as a likely Annexin-A2 target using enrichment analysis on a 2K1C microarray dataset and identifying several binding sites in the regulatory region of the mRNA. Expression analysis showed that ANGII increases NFAT5 protein but not mRNA level and, thus, indicated that NFAT5 is regulated by post-transcriptional regulation, which correlates with activation of the RNA-binding protein Annexin-A2. In conclusion, we show that ANGII increases Annexin-A2 nucleic acid binding activity that correlates with elevated protein levels of the NFAT5 transcription factor. NFAT signalling appears to be a major contributor to renal gene regulation in high-renin states.
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This article is a good source of information and a good way to become familiar with topics such as:
Angiotensin II;Annexin-A2;Hypertension;Kidney damage;NFAT
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