The Renin Angiotensin Angiotensinogen System (RAAS) has become a target to control the development and progression of hypertension. My laboratory is keen to reveal new targets that could aid in the development of therapeutics to control oxidative stress, kidney injury and high blood pressure in this devastating disease using unique approaches. My laboratory found a new function for the transcriptional regulator Sox6 in renin expression during juxtaglomerular cell recruitment and renal artery stenosis induced renovascular hypertension, oxidative stress and kidney damage. We are developing an innovative approach that includes: 1) the generation of a transgenic mouse, the C57BL6 Ren1dCre/Sox6fl/fl, which lacks the expression of Sox6 in renin expressing cells; 2) human induced pluripotent stem cells derived kidney organoids to establish the mechanism of renin expression control by Sox6; 3) mice cage systems that capture synchronized metabolic information, coupled to 4) biochemical and cellular assays. It is known that RASten frequency increases in elderly patients, and affects patients with diabetes, aortoiliac occlusive disease, coronary artery disease (CAD), or hypertension. This proposal will advance our understanding of the biological factors involved in the kidney response during renovascular hypertension and the role of the Sox6-Renin-prorenin-prorenin receptor axis during renal artery stenosis. Discerning the link between Sox6 and renin may uncover a new therapeutic target for the treatment of hypertension and kidney injury induced by renal artery stenosis as well as kidney damage induced by oxidative stress, a prevalent insult on other kidney and cardiovascular diseases.