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Literature Update：

Targeting the Downstream Signals of TLR4:

A New Approach for the Treatment of Diabetic Nephropathy

Literature Update
Journal of Advanced Research  /  IF：13.0

Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

Affiliations:Qilu Hospital, Shandong University

DOI: https://doi.org/10.1016/j.jare.2025.07.013

Product Citation:

Mouse IL-6 ELISA Kit（RE3186M）
Mouse IL-1β ELISA Kit（RE1074M）

Abstract:

This study investigated the regulatory role and mechanism of Toll-like receptor 4 (TLR4) in diabetic podocyte injury. 
It was found that TLR4 expression was upregulated in high-glucose-stimulated podocytes and streptozotocin (STZ)-induced diabetic renal tissues. Mechanistically, high glucose activates the TLR4/MyD88 signaling pathway, initiates the downstream PKCδ/SHP-1 signaling cascade, triggers endoplasmic reticulum stress and release of the inflammatory factor MCP-1, leading to structural damage to the podocyte slit diaphragm (SD), cytoskeletal disruption, and inflammatory responses. Podocyte-specific knockout of TLR4 alleviates podocyte injury and proteinuria by blocking the above-mentioned abnormalities, confirming the critical role of the TLR4/MyD88/PKCδ/SHP-1 axis in diabetic nephropathy and providing a theoretical basis for targeted TLR4 therapy.