Background: Renal artery stenosis (RAStenosis) or renal artery occlusion is an intractable problem affecting about 6% of people >65 and up to 40% of people with coronary or peripheral vascular disease in the Unites States. The renal renin-angiotensin-aldosterone system plays a key role in RAStenosis, with renin (which is mainly produced in the kidney) being recognized as the driver of the disease. In this study, we will determine a new function for the transcription factor Sox6 in the control of renal renin during RAStenosis. Methods: We hypothesize that knocking out Sox6 in Ren1d-positive cells will protect mice against renovascular hypertension and kidney injury. To test our hypothesis, we used a new transgenic mouse model, Ren1dcre/Sox6fl/fl (Sox6 KO), in which Sox6 is knocked out in renin-expressing cells. We used a modified two-kidney, one-clip (2K1C) Goldblatt mouse model to induce RAStenosis and renovascular hypertension. BP was measured using the tail-cuff method. Renin, prorenin, Sox6, and NGAL expressions levels were measured with Western blot, in situ hybridization, and immunohistochemistry. Creatinine levels were measured using the colorimetric assay. Results: Systolic BP was significantly lower in Sox6 KO 2 weeks after RAStenosis compared with Sox6 WT (Ren1dcre/Sox6wt/wt). Renin, prorenin, and NGAL expression levels in the stenosed kidney were lower in Sox6 KO compared with Sox6 WT mice. Furthermore, creatinine clearance was preserved in Sox6 KO compared with Sox6 WT mice. Conclusions: Our data indicate that Sox6 controls renal renin and prorenin expression and, as such, has a function in renovascular hypertension induced by RAStenosis. These results point to a novel transcriptional regulatory network controlled by Sox6.
Background: Renal artery stenosis (RAStenosis) or renal artery occlusion is an intractable problem affecting about 6% of people >65 and up to 40% of people with coronary or peripheral vascular disease in the Unites States. The renal renin-angiotensin-aldosterone system plays a key role in RAStenosis, with renin (which is mainly produced in the kidney) being recognized as the driver of the disease. In this study, we will determine a new function for the transcription factor Sox6 in the control of renal renin during RAStenosis. Methods: We hypothesize that knocking out Sox6 in Ren1d-positive cells will protect mice against renovascular hypertension and kidney injury. To test our hypothesis, we used a new transgenic mouse model, Ren1dcre/Sox6fl/fl (Sox6 KO), in which Sox6 is knocked out in renin-expressing cells. We used a modified two-kidney, one-clip (2K1C) Goldblatt mouse model to induce RAStenosis and renovascular hypertension. BP was measured using the tail-cuff method. Renin, prorenin, Sox6, and NGAL expressions levels were measured with Western blot, in situ hybridization, and immunohistochemistry. Creatinine levels were measured using the colorimetric assay. Results: Systolic BP was significantly lower in Sox6 KO 2 weeks after RAStenosis compared with Sox6 WT (Ren1dcre/Sox6wt/wt). Renin, prorenin, and NGAL expression levels in the stenosed kidney were lower in Sox6 KO compared with Sox6 WT mice. Furthermore, creatinine clearance was preserved in Sox6 KO compared with Sox6 WT mice. Conclusions: Our data indicate that Sox6 controls renal renin and prorenin expression and, as such, has a function in renovascular hypertension induced by RAStenosis. These results point to a novel transcriptional regulatory network controlled by Sox6.
Authors: E Singer; L Markó; N Paragas; J Barasch; D Dragun; D N Müller; K Budde; K M Schmidt-Ott Journal: Acta Physiol (Oxf) Date: 2013-02-04 Impact factor: 6.311
Authors: Toby Johnson; Tom R Gaunt; Stephen J Newhouse; Sandosh Padmanabhan; Maciej Tomaszewski; Meena Kumari; Richard W Morris; Ioanna Tzoulaki; Eoin T O'Brien; Neil R Poulter; Peter Sever; Denis C Shields; Simon Thom; Sasiwarang G Wannamethee; Peter H Whincup; Morris J Brown; John M Connell; Richard J Dobson; Philip J Howard; Charles A Mein; Abiodun Onipinla; Sue Shaw-Hawkins; Yun Zhang; George Davey Smith; Ian N M Day; Debbie A Lawlor; Alison H Goodall; F Gerald Fowkes; Gonçalo R Abecasis; Paul Elliott; Vesela Gateva; Peter S Braund; Paul R Burton; Christopher P Nelson; Martin D Tobin; Pim van der Harst; Nicola Glorioso; Hani Neuvrith; Erika Salvi; Jan A Staessen; Andrea Stucchi; Nabila Devos; Xavier Jeunemaitre; Pierre-François Plouin; Jean Tichet; Peeter Juhanson; Elin Org; Margus Putku; Siim Sõber; Gudrun Veldre; Margus Viigimaa; Anna Levinsson; Annika Rosengren; Dag S Thelle; Claire E Hastie; Thomas Hedner; Wai K Lee; Olle Melander; Björn Wahlstrand; Rebecca Hardy; Andrew Wong; Jackie A Cooper; Jutta Palmen; Li Chen; Alexandre F R Stewart; George A Wells; Harm-Jan Westra; Marcel G M Wolfs; Robert Clarke; Maria Grazia Franzosi; Anuj Goel; Anders Hamsten; Mark Lathrop; John F Peden; Udo Seedorf; Hugh Watkins; Willem H Ouwehand; Jennifer Sambrook; Jonathan Stephens; Juan-Pablo Casas; Fotios Drenos; Michael V Holmes; Mika Kivimaki; Sonia Shah; Tina Shah; Philippa J Talmud; John Whittaker; Chris Wallace; Christian Delles; Maris Laan; Diana Kuh; Steve E Humphries; Fredrik Nyberg; Daniele Cusi; Robert Roberts; Christopher Newton-Cheh; Lude Franke; Alice V Stanton; Anna F Dominiczak; Martin Farrall; Aroon D Hingorani; Nilesh J Samani; Mark J Caulfield; Patricia B Munroe Journal: Am J Hum Genet Date: 2011-11-17 Impact factor: 11.025
Authors: S Mistry; N Ives; J Harding; K Fitzpatrick-Ellis; G Lipkin; P A Kalra; J Moss; K Wheatley Journal: J Hum Hypertens Date: 2007-03-22 Impact factor: 3.012
Authors: Nattawat Klomjit; Sabena M Conley; Xiang Yang Zhu; Ishran M Sadiq; Yaara Libai; James D Krier; Christopher M Ferguson; Kyra L Jordan; Hui Tang; Amir Lerman; Lilach O Lerman Journal: Int J Obes (Lond) Date: 2022-03-07 Impact factor: 5.551