Abstract 045: Sox6 Has Protective Role During Renal Artery StenosisSInduced Hypertension

Abstract

Introduction: Renal artery stenosis is a common condition in patients with atherosclerosis. Narrowing of the renal arteries stimulate increases in renin production and release resulting in hypertension. Hypertension causes kidney injury and end organ damage. As such, there is much interest in developing novel treatments for the hypertension induced by renal artery stenosis. In renal artery stenosis, renin is a key disease driver. The objective of our study is to determine if the transcription factor Sox6 plays a role in renin induction of hypertension during renal artery stenosis. Methods: A novel transgenic mouse model (Ren1d Cre /Sox6 fl/fl -Sox6KO) was used to determine the impact of specific Sox6 ablation in renin expression after different stimuli. Ten days of low sodium diet (0.01% Na) and furosemide (0.1 mg/g body weight) was used to induce JG cell expansion. 2 Kidney 1 Clip (2K1C) Goldblatt model was used as renal artery stenosis model. Blood pressure was measured by tail-cuff method. Results: In wild-type mice renin and Sox6 expression increased during JG cell expansion. However, specific Sox6 ablation in renin expressing cells halted the increase in the number of JG cells (8.75 fold decrease, n= 6 to 9, P= 0.001). Furthermore, Sox6 KO mice were protected from developing hypertension and kidney damage after renal artery stenosis. Systolic blood pressure (116±2.13 and 132.9±3.3, n=9-10) and mean arterial pressure (103.3±1.9 and 121.5±1.01, n=9-10) were significantly lower in Sox6 KO compared to wild-type mice. When stenosed kidneys were compared, renin expression was higher in wild-type compared to Sox6 KO group as measured by immunoblotting (0.49 ± 0.05898, and 0.2266±0.02716; P =0.0358, n=2-3). Creatinine levels in urine were higher in wild-type group compared to Sox6 KO group (2382 ± 399 and 1804 ± 177.8, P =0.0358, n=9). Conclusion: Our data indicates that Sox6 plays a novel role in modulating renal renin expression during pathological conditions. These results suggest that Sox6 is a potential drug target for therapies which seek to control blood pressure in hypertensive patients.