Stimulator of Interferon Genes (STING) Deletion Alleviates Podocyte Injury Through Suppressing Inflammatory Response in Diabetic Kidney Disease
- Diabetic Kidney Disease: Basic - I
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
- Chen, Zhaowei, Renmin Hospital of Wuhan University, Wuhan, China
- Yang, Xueyan, Renmin Hospital of Wuhan University, Wuhan, China
- Ding, Guohua, Renmin Hospital of Wuhan University, Wuhan, China
The stimulator of interferon genes (STING) is an adaptor protein that can drive noninfectious inflammation and pyroptosis. NLRP3-mediated inflammasome activation is an important type of inflammatory programmed death with strong pro-inflammatory activity and has been confirmed to promote a chronic inflammatory response in DKD. However, the mechanism of STING regulating immune inflammation and the interaction with NLRP3-dependent pyroptosis in the high glucose (HG) state remains unknown. The present study aims to evaluate whether STING contributes to HG-induced podocyte inflammation response through modulating NLRP3-dependent pyroptosis.
In vivo study, co-localization expression of STING and synaptopodin was evaluated in glomeruli by double immunolabeling. Western blot was performed to assess STING and inflammatory-related protein expression in glomeruli. q-PCR was used to detect inflammatory molecule expression. Transmission electron microscope (TEM) was used to identify ultrastructure changes of podocytes in diabetic mice. Pathological changes were evaluated by periodic acid-Schiff stain (PAS) or hematoxylin and eosin (HE) staining. In vitro study, podocytes were exposed to HG (40mM) for 24 h. Immunofluorescence assay and western blot were performed to evaluate STING expression. Pyroptosis and inflammatory-related molecule expression were detected by western blot and q-PCR. STING siRNA was transfected to podocytes to evaluate the effect of STING inhibition on podocyte inflammatory response under HG stimulation.
Double immunolabeling of STING and synaptopodin in glomeruli was obviously increased in diabetic animals. In addition, STING protein expression was increased in diabetic mice compared with controls. Deletion of STING alleviated podocyte injury, renal dysfunction inflammation, NLRP3 inflammasome activation, and pyroptosis in diabetic mice. In cultured podocytes, STING protein expression was increased in HG-treated podocytes. Modulated STING expression by STING siRNA alleviated pyroptosis and NLRP3 inflammasome activation in HG-treated podocytes.
These results indicate that STING deletion suppresses podocytes inflammation response by targeting NLRP3 and provide evidence that STING may be a potential target for podocyte injury in DKD.