Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha.

The Journal of Biological Chemistry
Kenichi MatsushitaVictor J Dzau

Abstract

Renin is a key enzyme for cardiovascular and renal homeostasis and is produced by highly specialized endocrine cells in the kidney, known as juxtaglomerular (JG) cells. The nature and origin of these cells remain as mysteries. Previously, we have shown that the nuclear hormone receptor liver X receptor-alpha (LXRalpha) is a major transcriptional regulator of the expression of renin, c-myc, and other genes involved with growth/differentiation. In this study we test the hypothesis that LXRalpha plays an important role not only in renin expression but also in renin-containing cell differentiation, specifically from the mesenchymal stem cell (MSC), which may be the origin of the JG cell. Indeed, our data demonstrated that LXRalpha activation by its ligands or cAMP stimulated renin gene expression in both murine and human MSCs. Furthermore, sustained cAMP stimulation of murine MSCs overexpressing LXRalpha led to their differentiation into JG-like cells expressing renin and alpha-smooth muscle actin. These MSC-derived JG-like cells contained renin in secretory granules and released active renin in response to cAMP. In conclusion, the activation of LXRalpha stimulates renin expression and induces MSCs differentiation into renin-secret...Continue Reading

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Citations

May 12, 2012·Pflügers Archiv : European journal of physiology·Sean T GlennLi Pan
Apr 17, 2013·Pflügers Archiv : European journal of physiology·Ania StefańskaJ J Mullins
May 3, 2012·Clinical Science·Matej DurikAnton J M Roks
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May 24, 2017·Pflügers Archiv : European journal of physiology·Peter LachmannVladimir T Todorov
Mar 27, 2020·American Journal of Physiology. Cell Physiology·Lan ChenMasanori Abe
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Apr 18, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Kenichi Matsushita, Victor J Dzau
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Patricia Kauanna Fonseca DamascenoMilena Botelho Pereira Soares

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