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Modified Citrus Pectin Alleviates Diabetic Kidney Disease by Suppressing Pyroptosis in Renal Tubular Epithelial Cells
Qi Wu1, Yubo Guan2, Yijing Li3
1Department of Physiology, School of the Basic Medicine, Xuzhou Medical University, Xuzhou, China.
Abstract:
Modified citrus pectin (MCP) exhibits antioxidant properties, while persistent oxidative stress is one of the key mechanisms contributing to the progression of diabetic kidney disease (DKD). However, its role and underlying mechanisms in the progression of DKD remain inadequately understood. The objective is to clarify the functions of MCP in the regulation of renal tubular epithelial cell injury and to substantiate the underlying mechanisms. For in vivo experiments, C57BL/6J mice and db/db mice were used to verify the role of MCP. Normal rat renal tubular epithelial cells (NRK-52E) and Connexin 43 (Cx43+/-) NRK-52E were used to investigate the mechanism of MCP in in vitro. MCP ameliorated serum creatinine, urine protein, and renal interstitial damage in db/db mice, inhibited the expression of P-extracellular signal-regulated kinase (P-ERK) and Gasdermin D-NT(GSDMD-NT) proteins in renal tissue and improved the changes in indicators such as reactive oxygen species(ROS)/ , P-ERK, thioredoxin-interacting protein(Txnip), thioredoxin 1(Trx1), and Cx43 induced by Px12. MCP inhibited renal tubular epithelial cells pyroptosis via the Cx43-ERK1/2 signaling pathway.
Insights
Modified citrus pectin (MCP) can protect against diabetic kidney disease (DKD) progression by reducing kidney damage and inhibiting cell death. This study clarifies MCP
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes, characterized by persistent oxidative stress and renal tubular epithelial cell injury.
- Modified citrus pectin (MCP) possesses antioxidant properties, but its specific role and mechanisms in DKD progression are not fully understood.
Purpose of the Study:
- To investigate the protective effects of MCP on renal tubular epithelial cells in DKD.
- To elucidate the underlying molecular mechanisms by which MCP regulates cell injury and pyroptosis in DKD.
Main Methods:
- In vivo studies utilized C57BL/6J and db/db mice to assess MCP's efficacy.
- In vitro experiments employed normal rat renal tubular epithelial cells (NRK-52E) and Connexin 43 (Cx43+/-) NRK-52E cells to explore mechanisms.
- Key indicators measured included serum creatinine, urine protein, renal interstitial damage, reactive oxygen species (ROS), P-extracellular signal-regulated kinase (P-ERK), Gasdermin D-NT (GSDMD-NT), thioredoxin-interacting protein (Txnip), thioredoxin 1 (Trx1), and Cx43.
Main Results:
- MCP treatment ameliorated kidney damage markers (serum creatinine, urine protein) and renal interstitial damage in db/db mice.
- MCP inhibited the expression of P-ERK and GSDMD-NT in renal tissue.
- In vitro, MCP improved ROS levels and modulated the expression of P-ERK, Txnip, Trx1, and Cx43, thereby inhibiting pyroptosis via the Cx43-ERK1/2 signaling pathway.
Conclusions:
- Modified citrus pectin demonstrates significant renoprotective effects in diabetic kidney disease.
- MCP mitigates renal tubular epithelial cell pyroptosis through the Cx43-ERK1/2 signaling pathway, highlighting its therapeutic potential for DKD.
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