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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.
Objective:
Diabetic nephropathy is one of the most important microvascular complications of diabetes, which mainly refers to glomerular capillary sclerosis. Podocytes are an important part of glomerular capillaries. Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy. This study aimed to assess the protective mechanism of glycyrrhizic acid (GA) on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5'-monophosphate-activated protein kinase (AMPK)/sucrose nonfermenting AMPK-related kinase (SNARK) signaling pathway.
Methods:
SNARK siRNA was used to transfect podocytes. Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis. The expression levels of key pathway proteins (including TGF-β1, α-SMA, SITR1, AMPKα, LKB1, PGC-1α, NF-κB, IL-6, and TNF-α) were verified by Western blotting. The expression of inflammatory factors in podocytes was detected by ELISA.
Results:
We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors. However, after transfection of podocytes with SNARK siRNA, there was an increased expression of fibrosis-related factors and inflammation-related factors.
Conclusion:
GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose, which is related to the AMPK signaling pathway. Meanwhile, knockdown of SNARK protein can inhibit the AMPK signaling pathway, aggravate fibrosis, and increase inflammation.
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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