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Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
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Published on: June 7, 2016

Products of 12/15-lipoxygenase upregulate the angiotensin II receptor

Zhong-Gao Xu1, Hang Yuan, Linda Lanting

  • 1Gonda Diabetes Research Center, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.

Journal of the American Society of Nephrology : JASN
|February 1, 2008
PubMed

Insights

Oxidized lipids from the 12/15-lipoxygenase pathway increase angiotensin II type 1 receptor (AT1R) expression in kidney cells. This enhances angiotensin II

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Angiotensin II type 1 receptor (AT1R) and the 12/15-lipoxygenase pathway are implicated in diabetic nephropathy.
  • The regulatory relationship between 12/15-lipoxygenase and AT1R expression is not well understood.

Purpose of the Study:

  • To investigate whether 12/15-lipoxygenase regulates AT1R expression in the context of diabetic nephropathy.

Main Methods:

  • Utilized cultured rat mesangial cells and mesangial cells/glomeruli from 12/15-lipoxygenase knockout mice.
  • Employed short hairpin RNA (shRNA) and siRNA to modulate 12/15-lipoxygenase levels.
  • Assessed AT1R mRNA and protein expression, and angiotensin II signaling effects.
  • Examined effects in a diabetic mouse model.

Main Results:

  • 12/15-lipoxygenase product 12(S)-HETE increased AT1R mRNA and protein by stabilizing AT1R mRNA.
  • Knockdown or knockout of 12/15-lipoxygenase decreased AT1R expression.
  • Overexpression of 12/15-lipoxygenase increased AT1R expression.
  • siRNA targeting 12/15-lipoxygenase reduced glomerular AT1R in diabetic mice.
  • Angiotensin II induced greater profibrotic markers in AT1R-overexpressing cells.

Conclusions:

  • Oxidized lipids generated by 12/15-lipoxygenase enhance AT1R expression in mesangial cells.
  • This mechanism augments the profibrotic effects of angiotensin II in diabetic nephropathy.

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