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Inhibitory effects of peroxisome proliferator-activated receptor γ agonists on collagen IV production in podocytes

Yanjiao Li1, Yachen Shen, Min Li

  • 1Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, 030012, Shanxi, China.

Molecular and Cellular Biochemistry
|April 30, 2015
PubMed

Insights

Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, like rosiglitazone and pioglitazone, inhibit collagen IV production in mouse podocytes. This mechanism supports their protective role in kidney diseases by reducing glomerulosclerosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists show promise in treating kidney diseases by reducing microalbuminuria and glomerulosclerosis.
  • The precise molecular mechanisms behind these renoprotective effects are not fully elucidated.
  • Understanding how PPAR-γ agonists impact podocyte function is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the effect of PPAR-γ agonists, rosiglitazone (Rosi) and pioglitazone (Pio), on collagen IV production in mouse podocytes.
  • To elucidate the underlying molecular pathways involved in PPAR-γ-mediated regulation of collagen IV expression.
  • To explore the role of TGF-β signaling and Smad phosphorylation in this process.

Main Methods:

  • Primary mouse podocytes were treated with PPAR-γ agonists (Rosi, Pio) and antagonist (GW9662).
  • Collagen IV expression and production were assessed using RT-PCR and Western blot.
  • TGF-β-induced signaling pathways, including Smad2/3 phosphorylation and SBE4-luciferase activity, were analyzed.

Main Results:

  • Endogenous PPAR-γ was detected in podocytes and upregulated by Rosi and Pio.
  • PPAR-γ agonists significantly inhibited TGF-β-induced collagen IV expression and production.
  • Inhibition of collagen IV was reversed by a PPAR-γ antagonist, confirming the agonist's role.
  • Pio treatment attenuated TGF-β-induced Smad2/3 phosphorylation and collagen IV gene promoter activity.
  • PPAR-γ activation directly suppresses collagen IV synthesis in podocytes.

Conclusions:

  • PPAR-γ activation by agonists like rosiglitazone and pioglitazone directly inhibits collagen IV expression and synthesis in mouse podocytes.
  • This inhibitory effect is mediated through the suppression of TGF-β-induced Smad2/3 phosphorylation and reduced activity of Smad-binding elements in the collagen IV gene promoter.
  • These findings provide a novel mechanistic basis for the podocyte-protective effects of PPAR-γ agonists in kidney disease.

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