1. Sox6 as a new modulator of renin expression in the kidney
- Author
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Maria Mirotsou, Victor J. Dzau, Alan Payne, Vivian Gama, Conrad P. Hodgkinson, Jason D. Foss, Megan L. Rasmussen, Mohammad Saleem, Liang Xiao, Juan Antonio Giménez-Bastida, and Jose A Gomez
- Subjects
Male ,medicine.medical_specialty ,Afferent arterioles ,Physiology ,Myocytes, Smooth Muscle ,Blood Pressure ,Muscle, Smooth, Vascular ,Smooth muscle ,Furosemide ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,Diuretics ,Cells, Cultured ,Cell Proliferation ,Mice, Knockout ,Kidney ,Chemistry ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Diet, Sodium-Restricted ,Juxtaglomerular Apparatus ,Mice, Inbred C57BL ,Arterioles ,Endocrinology ,Blood pressure ,medicine.anatomical_structure ,Gene Expression Regulation ,SOXD Transcription Factors ,Signal Transduction ,Research Article - Abstract
Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells that give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation, renal mesenchymal stromal cells (MSCs) differentiate from JG cells. JG cells undergo expansion and smooth muscle cells redifferentiate to express renin along the afferent arteriole. Gene expression profiling comparing resident renal MSCs with JG cells indicates that the transcription factor Sox6 is highly expressed in JG cells in the adult kidney. In vitro, loss of Sox6 expression reduces differentiation of renal MSCs to renin-producing cells. In vivo, Sox6 expression is upregulated after a low-Na+ diet and furosemide. Importantly, knockout of Sox6 in Ren1d+ cells halts the increase in renin-expressing cells normally seen during a low-Na+ diet and furosemide as well as the typical increase in renin. Furthermore, Sox6 ablation in renin-expressing cells halts the recruitment of smooth muscle cells along the afferent arteriole, which normally express renin under these conditions. These results support a previously undefined role for Sox6 in renin expression.
- Published
- 2020
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