Glycyrrhizic Acid Protects Glomerular Podocytes Induced by High Glucose by Modulating SNARK/AMPK Signaling Pathway

Tian-Qi Zhao1, Yuan Li2, Miao Zhang3

  • 1School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, China.

PubMed
Abstract

Insights

Glycyrrhizic acid (GA) protects kidney podocytes from high glucose damage by activating the AMPK pathway, reducing fibrosis and inflammation. Inhibiting SNARK protein worsens these effects, highlighting GA

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic nephropathy is a major complication of diabetes, characterized by glomerular sclerosis.
  • Podocyte injury and fibrosis are key pathological features of diabetic nephropathy.
  • The adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway is implicated in cellular protection.

Purpose of the Study:

  • To investigate the protective mechanism of glycyrrhizic acid (GA) on high glucose-induced podocyte injury.
  • To determine if GA exerts antifibrotic and anti-inflammatory effects via the AMPK/sucrose nonfermenting AMPK-related kinase (SNARK) signaling pathway.

Main Methods:

  • Podocytes were transfected with SNARK siRNA.
  • Gene and protein expression analysis using real-time quantitative PCR, immunofluorescence, Western blotting, and ELISA.
  • Key factors in fibrosis (TGF-β1, α-SMA) and inflammation (NF-κB, IL-6, TNF-α) were assessed.

Main Results:

  • Glycyrrhizic acid (GA) upregulated the AMPK pathway, decreasing fibrosis-related factors in podocytes.
  • SNARK siRNA transfection inhibited the AMPK pathway, leading to increased fibrosis and inflammation.
  • GA treatment reduced inflammatory markers, while SNARK knockdown exacerbated inflammation.

Conclusions:

  • Glycyrrhizic acid (GA) protects podocytes against high glucose-induced fibrosis and inflammation through the AMPK signaling pathway.
  • SNARK plays a crucial role in this pathway; its inhibition aggravates podocyte damage.
  • GA represents a potential therapeutic agent for diabetic nephropathy.

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