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

Publication ,  Journal Article
Matsushita, K; Morello, F; Wu, Y; Zhang, L; Iwanaga, S; Pratt, RE; Dzau, VJ
Published in: J Biol Chem
April 16, 2010

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-secreting, JG-like cells. Our results suggest that the MSC may be the origin of the juxtaglomerular cell and provide insight into novel understanding of pathophysiology of the renin-angiotensin system.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

April 16, 2010

Volume

285

Issue

16

Start / End Page

11974 / 11982

Location

United States

Related Subject Headings

  • Renin-Angiotensin System
  • Renin
  • Recombinant Fusion Proteins
  • RNA, Small Interfering
  • Orphan Nuclear Receptors
  • Models, Biological
  • Mice, Inbred C57BL
  • Mice
  • Mesenchymal Stem Cells
  • Liver X Receptors
 

Citation

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MLA
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Matsushita, K., Morello, F., Wu, Y., Zhang, L., Iwanaga, S., Pratt, R. E., & Dzau, V. J. (2010). Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha. J Biol Chem, 285(16), 11974–11982. https://doi.org/10.1074/jbc.M109.099671
Matsushita, Kenichi, Fulvio Morello, Yaojiong Wu, Lunan Zhang, Shiro Iwanaga, Richard E. Pratt, and Victor J. Dzau. “Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha.J Biol Chem 285, no. 16 (April 16, 2010): 11974–82. https://doi.org/10.1074/jbc.M109.099671.
Matsushita K, Morello F, Wu Y, Zhang L, Iwanaga S, Pratt RE, et al. Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha. J Biol Chem. 2010 Apr 16;285(16):11974–82.
Matsushita, Kenichi, et al. “Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha.J Biol Chem, vol. 285, no. 16, Apr. 2010, pp. 11974–82. Pubmed, doi:10.1074/jbc.M109.099671.
Matsushita K, Morello F, Wu Y, Zhang L, Iwanaga S, Pratt RE, Dzau VJ. Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha. J Biol Chem. 2010 Apr 16;285(16):11974–11982.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

April 16, 2010

Volume

285

Issue

16

Start / End Page

11974 / 11982

Location

United States

Related Subject Headings

  • Renin-Angiotensin System
  • Renin
  • Recombinant Fusion Proteins
  • RNA, Small Interfering
  • Orphan Nuclear Receptors
  • Models, Biological
  • Mice, Inbred C57BL
  • Mice
  • Mesenchymal Stem Cells
  • Liver X Receptors