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Kidney Week

Abstract: FR-OR080

Sox6 Ablation in Renin Expressing Cells Has Protective Function Against Renovascular Hypertension and Kidney Damage

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Saleem, Mohammad, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Xiao, Liang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Saavedra, Luz A., VUMC, Nashville, Tennessee, United States
  • Gomez, Jose, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background


Renal artery stenosis (RAStenosis) is an interactable problem affecting about 6% of the people over 65 and in up to 40% of the people with coronary or peripheral vascular disease. The renin angiotensin aldosterone system (RAAS) is implicated in RAStenosis. Renin controls rate-limiting step in RAAS and is a key driver in RAStenosis induced hypertension. Sox6 is a transcription factor important for cell fate determination of muscle, bone, neurons among others.

Methods

A new transgenic mice the Ren1dCre/Sox6fl/fl (Sox6 KO), in which Sox6 is knockout in renin expressing cells was used to determine the impact of Sox6 ablation on renin expression and hypertension during RAStenosis. Two time-point studies, 3 weeks, and 3 days were conducted. Blood pressure was measured by tail-cuff method. The kidney injury markers KIM1, creatinine, albumin, and urea were measured using commercially available kits. Superoxide was measured using HPLC.

Results

In 3-week study; systolic and mean arterial blood pressure were significantly lower in Sox6 KO compared to wild-type mice. When stenosed kidneys were compared, renin expression levels were significantly lower in Sox6 KO compared to wild-type. Urine creatinine clearance was significantly higher in Sox6 KO compared to wild-type. In 3-day study; renin, STAT3, HIF1-α, N-Gal, and Sox6 serine-threonine phosphorylation levels were lower in the stenosed kidney of Sox6 KO compared to wild-type. This indicates that phosphorylated Sox6 triggers renin expression increase in RAStenosis and indicates that HIF1-a and STAT3 may control Sox6 expression in RAStenosis. Superoxide levels in stenosed kidney were lower in Sox6 KO compared to wild-type mice. Urine creatinine clearance was significantly higher in Sox6 KO compared to wild-type animals. KIM1, urea, and albumin levels were not different between the groups in both time-point. Altogether, our data suggest that Sox6 KO mice were protected from developing hypertension and kidney damage during RAStenosis.

Conclusion

Our data indicates that Sox6 has a new function modulating renin expression, renovascular hypertension and kidney damage induced by RAStenosis. Identification of this novel pathway and its regulators may lead to new therapies for hypertension and associated cardiovascular disease.

Funding

  • Other NIH Support