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Advanced glycation end-products activate the renin-angiotensin system through the RAGE/PI3-K signaling pathway in

Cailan L Cheng1, Ying Tang, Zhenda Zheng

  • 1Department of Nephrology, The third Affliated Hospital of SunYat-Sen University, Guangzhou, Guangdong, China.

Clinical and Investigative Medicine. Medecine Clinique Et Experimentale
|October 10, 2012
PubMed
Abstract

Insights

Advanced glycation end-products (AGEs) activate the kidney

Area of Science:

  • Nephrology and cellular biology
  • Molecular mechanisms of kidney disease
  • Renal pathophysiology

Background:

  • Advanced glycation end-products (AGEs) are implicated in diabetic nephropathy.
  • The renin-angiotensin system (RAS) plays a critical role in kidney function and disease.
  • Podocytes are essential for maintaining the filtration barrier in the kidneys.

Purpose of the Study:

  • To investigate the impact of AGEs on the renin-angiotensin system (RAS) components within podocytes.
  • To elucidate the underlying molecular mechanisms by which AGEs affect podocyte RAS.

Main Methods:

  • Cultured immortalized mouse podocytes were treated with varying concentrations and durations of AGEs.
  • Expression levels of angiotensinogen (AGT), AT1R, AT2R, and renin were quantified using real-time PCR and Western blot.
  • Receptor for AGEs (RAGE), Akt, phosphorylated Akt, Angiotensin II (Ang II), and angiotensin-converting enzyme (ACE) activity were assessed.

Main Results:

  • AGEs significantly upregulated AGT and AT1R expression, alongside increased Ang II levels and ACE activity in podocytes.
  • AGEs also elevated RAGE expression and Akt phosphorylation, indicating activation of the RAGE-PI3-K/Akt pathway.
  • Inhibition of RAGE or PI3-K pathways attenuated AGEs-induced increases in AGT, AT1R, Ang II, and ACE activity.

Conclusions:

  • AGEs activate the renin-angiotensin system (RAS) in podocytes via a RAGE-PI3-K/Akt-dependent pathway.
  • This activation contributes to increased podocyte apoptosis.
  • Targeting the RAGE-PI3-K/Akt pathway may offer therapeutic strategies for AGEs-related kidney damage.

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