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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Resveratrol prevents Drp1-mediated mitochondrial fission in the diabetic kidney through the PDE4D/PKA pathway

Xia Zhu1, Zongli Deng1, Yanjuan Cao1

  • 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

Phytotherapy Research : PTR
|September 28, 2023
PubMed

Insights

Resveratrol protects against diabetic nephropathy (DN) by inhibiting phosphodiesterase 4D (PDE4D), reducing mitochondrial fragmentation, and restoring key protein levels. This highlights PDE4D as a therapeutic target for DN.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Diabetic nephropathy (DN) is a major complication of diabetes, characterized by progressive renal fibrosis.
  • The role of phosphodiesterase 4D (PDE4D) in DN pathogenesis and the potential therapeutic effects of resveratrol are not fully understood.

Purpose of the Study:

  • To investigate the role of PDE4D in DN.
  • To determine if resveratrol exerts protective effects against DN by inhibiting PDE4D.

Main Methods:

  • Utilized diabetic db/db mice and human glomerular mesangial cells (GMCs) exposed to high glucose (HG).
  • Assessed the effects of resveratrol on DN progression, mitochondrial morphology, and expression of PDE4D, PKA, and Drp1.
  • Investigated the impact of PDE4D overexpression and PKA inhibition on resveratrol's protective mechanisms.

Main Results:

  • Resveratrol alleviated DN progression in db/db mice by inhibiting mitochondrial fragmentation and modulating PDE4D, PKA, and Drp1 expression.
  • In HG-treated GMCs, resveratrol reduced PDE4D expression, increased PKA, and inhibited Drp1-mediated mitochondrial fission.
  • Overexpression of PDE4D counteracted resveratrol's protective effects, while PKA inhibition mimicked these effects, indicating PDE4D/PKA/Drp1 pathway involvement.

Conclusions:

  • PDE4D plays a significant role in the development of diabetic nephropathy.
  • Resveratrol attenuates DN by inhibiting PDE4D, which prevents mitochondrial fission and regulates phosphorylated Drp1-Ser637 expression.
Keywords:
Drp1PDE4DPKAdiabetic nephropathyresveratrol

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