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Abstract: FR-PO342

A New Role of Sox6 in Blood Pressure Regulation

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Saleem, Mohammad, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hodgkinson, Conrad, Duke University, Durham, North Carolina, United States
  • Gomez, Jose, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Hypertension afflicts about 50% of the U.S. adult population, of which half are unresponsive to treatment. As such, new therapies to treat this disease and its complications are necessary. Renin catalyzes the rate limiting step in the renin angiotensin aldosterone system (RAAS) and is produced and stored by Juxtaglomerular (JG) cells in the kidney. The transcriptional mechanisms that govern renin expression are of great importance to develop new treatments for hypertension. Gene expression profiling indicated that the transcription factor Sox6 is highly expressed in JG cells compared to renal Mesenchymal Stromal Cells (MSCs) in the adult kidney. Moreover, in vitro Sox6 knockdown decreased the differentiation of renal MSCs into renin producing cells. These results support a previously undefined role for Sox6 in blood pressure control. Several human genetic studies associate Sox6 with hypertension. We hypothesized that Sox6 is a new transcription factor involved in renin expression control.

Methods

Ren1dCre/Sox6fl/fl (Sox6KO mouse), in which Sox6 is deleted specifically in renin expressing cells was used. In vivo: JG cell expansion was induced by 10 days of low sodium diet (0.01% Na) and furosemide (0.1 mg/g body weight). Plasma renin concentration measured by elisa. Expression of genes involved in vasoconstriction, calcium (Ca2+) and sodium (Na) metabolism was measured by qRT-PCR.

Results

In vivo, at base line specific Sox6 knock-out animals did not alter plasma renin concentration (575±492 ng/mL Sox6-wt vs 984±400 ng/mL Sox6-KO, N=7-11). However, the expression of several genes involved in vasoconstriction, Ca2+ and Na metabolism were solely expressed in the Sox6-KO mice. In contrast to the basal state, Sox6 knockout had a dramatic effect during JG cell expansion. As expected, in wild-type mice plasma renin concentration increased during JG cell expansion. Interestingly, there was a concomitant increase in Sox6 expression. In contrast, specific knock out of Sox6 in renin expressing cells halted the increase in the amount of plasma renin concentration during JG cell expansion (186±123 ug/mL Sox6-wt vs 135±68 ug/mL Sox6-KO, N=17-18, P<0.05).

Conclusion

These results support a novel role of Sox6 in renin cell fate and thereby in renal development and blood pressure regulation. This opens new possibilities of renin regulation and the development of new therapeutic targets for hypertension.

Funding

  • Other NIH Support