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Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes.

Publication ,  Journal Article
Matsushita, K; Wu, Y; Okamoto, Y; Pratt, RE; Dzau, VJ
Published in: Hypertension
December 2006

Clinical and experimental evidence suggest that the renin-angiotensin system (RAS) plays a role in metabolic syndrome. Adipogenesis is suggested to modulate obesity and obesity-related consequences, such as metabolic syndrome. Although mesenchymal stem cells (MSCs) are a major source of adipocyte generation, the influence of RAS on MSC differentiation to adipocyte is unknown. We evaluated the expression of endogenous RAS in human MSCs during its differentiation to adipocytes and studied the effects of angiotensin II (Ang II), Ang II type 1 receptor blocker Valsartan, and type 2 (AT(2)) receptor blocker PD123319. Our data showed that differentiation was associated with an increase in cellular renin and AT(2) receptor expression and a concomitant decrease in angiotensinogen and angiotensin-converting enzyme expression. The net effect is an increase in endogenous cellular angiotensin II production. Incubation with Ang II (exogenous) inhibited adipogenesis. Combined treatment of exogenous Ang II and Valsartan further inhibited adipogenesis, whereas combined treatment of Ang II and PD123319 completely abolished the inhibition of adipogenesis, suggesting an important role for the AT(2) receptor. Blockade of endogenous angiotensin II effect by incubation with Valsartan alone inhibited adipogenesis, whereas PD123319 alone promoted adipogenesis, confirming the data using exogenous Ang II. The combination of Valsartan and PD123319 had no net effect. Our data demonstrate an important role of the expression of the local RAS in the regulation of human MSC differentiation to adipocytes. Elucidation of the molecular mechanism should provide important insight into the pathophysiology of the metabolic syndrome and the development of future therapeutics.

Duke Scholars

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

December 2006

Volume

48

Issue

6

Start / End Page

1095 / 1102

Location

United States

Related Subject Headings

  • Valsartan
  • Valine
  • Tetrazoles
  • Renin-Angiotensin System
  • Renin
  • Receptors, Angiotensin
  • Pyridines
  • Mesenchymal Stem Cells
  • Imidazoles
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Matsushita, K., Wu, Y., Okamoto, Y., Pratt, R. E., & Dzau, V. J. (2006). Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes. Hypertension, 48(6), 1095–1102. https://doi.org/10.1161/01.HYP.0000248211.82232.a7
Matsushita, Kenichi, Yaojiong Wu, Yoshihisa Okamoto, Richard E. Pratt, and Victor J. Dzau. “Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes.Hypertension 48, no. 6 (December 2006): 1095–1102. https://doi.org/10.1161/01.HYP.0000248211.82232.a7.
Matsushita K, Wu Y, Okamoto Y, Pratt RE, Dzau VJ. Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes. Hypertension. 2006 Dec;48(6):1095–102.
Matsushita, Kenichi, et al. “Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes.Hypertension, vol. 48, no. 6, Dec. 2006, pp. 1095–102. Pubmed, doi:10.1161/01.HYP.0000248211.82232.a7.
Matsushita K, Wu Y, Okamoto Y, Pratt RE, Dzau VJ. Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes. Hypertension. 2006 Dec;48(6):1095–1102.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

December 2006

Volume

48

Issue

6

Start / End Page

1095 / 1102

Location

United States

Related Subject Headings

  • Valsartan
  • Valine
  • Tetrazoles
  • Renin-Angiotensin System
  • Renin
  • Receptors, Angiotensin
  • Pyridines
  • Mesenchymal Stem Cells
  • Imidazoles
  • Humans