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Emerging Mechanistic Roles of STING Signaling in Kidney Diseases
Chenjian Gu1, Ying Maggie Chen2
1Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
The American Journal of Pathology
|December 18, 2025
Summary
Stimulator of interferon genes (STING) protein has roles beyond immunity, impacting kidney health. Aberrant STING activation is linked to various kidney diseases, suggesting it as a potential drug target.
Area of Science:
- Immunology
- Cell Biology
- Nephrology
Background:
- Stimulator of interferon genes (STING) is an endoplasmic reticulum-anchored protein crucial for innate immunity against DNA.
- STING also performs noncanonical functions, including regulating autophagy, calcium homeostasis, and secretory pathway integrity.
Purpose of the Study:
- To review the diverse functions of STING beyond interferon signaling.
- To highlight STING's emerging role in kidney disease pathogenesis.
- To underscore STING as a potential therapeutic target for kidney disorders.
Main Methods:
- Literature review of recent research on STING function and kidney disease.
- Analysis of studies investigating STING's noncanonical roles.
- Synthesis of findings linking STING activation to various kidney pathologies in murine models.
Main Results:
- STING modulates autophagy, ER-mitochondrial calcium, ER stress response, and Golgi function.
- Aberrant STING activation is associated with acute kidney injury, CKD, and genetic kidney diseases in mice.
- STING's noncanonical functions are increasingly implicated in kidney disease development.
Conclusions:
- STING possesses significant noncanonical functions impacting cellular processes relevant to kidney health.
- STING activation is a key factor in the pathogenesis of multiple kidney disorders.
- Targeting STING presents a promising therapeutic strategy for kidney disease treatment.
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