Related Experiment Video
Updated: Aug 21, 2026
Mouse Electroacupuncture Fixation Device Fabrication for Electroacupuncture Pretreatment in Diabetic Cardiomyopathy Mouse Model
Published on: April 18, 2025
IL-38 attenuates diabetic cardiomyopathy by regulating NLRP3-mediated pyroptosis via the STING signaling pathway
Xiao Wei1, Yan Liu1, Donghui An1
1Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang 050000, China.
Insights
Interleukin-38 (IL-38) protects against diabetic cardiomyopathy (DCM) by reducing inflammation and pyroptosis, a form of cell death. This study shows IL-38 alleviates heart damage in type 2 diabetes by modulating the STING/NLRP3 pathway.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cellular Biology
Background:
- Diabetic cardiomyopathy (DCM) involves cardiac remodeling, fibrosis, and dysfunction, driven by chronic inflammation.
- Pyroptosis, a pro-inflammatory programmed cell death, significantly contributes to myocardial inflammation in DCM.
- Interleukin-38 (IL-38) possesses anti-inflammatory properties, suggesting a potential therapeutic role in inflammatory conditions.
Purpose of the Study:
- To investigate the protective effects of IL-38 against diabetes-induced myocardial injury.
- To determine if IL-38 modulates pyroptosis in the context of diabetic cardiomyopathy.
- To elucidate the underlying signaling pathways, specifically the STING/NLRP3 cascade, involved in IL-38's action.
Main Methods:
- Type 2 diabetes was induced in mice, followed by IL-38 treatment, with assessments of cardiac function, histology, and apoptosis.
- Pyroptosis-related protein levels and signaling pathways were evaluated in vivo and in vitro using cultured cardiomyocytes.
- The impact of NLRP3 overexpression and STING pathway activation on IL-38's efficacy was examined.
Main Results:
- IL-38 administration significantly ameliorated myocardial damage and cardiac dysfunction in diabetic mice.
- IL-38 suppressed pyroptosis by downregulating pyroptosis-associated proteins in diabetic hearts.
- IL-38 exerted its protective effects through the modulation of the STING/NLRP3 signaling pathway, although excessive NLRP3 or STING activation diminished these benefits.
Conclusions:
- IL-38 demonstrates significant therapeutic potential for diabetic cardiomyopathy by mitigating inflammation and pyroptosis.
- The anti-pyroptotic and cardioprotective effects of IL-38 are mediated via regulation of the STING/NLRP3 signaling axis.
- Targeting IL-38 may offer a novel strategy for managing diabetic cardiomyopathy, contingent on the modulation of specific inflammatory pathways.
Abstract:
Diabetic cardiomyopathy (DCM) represents a distinctive myocardial disorder marked by detrimental structural remodeling, encompassing cardiac hypertrophy, myocardial fibrosis, compromised coronary microvascular perfusion, and myocardial dysfunction. Pyroptosis, a newly recognized form of programmed cell death, correlates with inflammatory responses. Chronic inflammation serves a pivotal function in DCM, with pyroptosis substantially contributing to myocardial inflammation in this pathological state. IL-38 demonstrates anti-inflammatory properties through the inhibition of inflammatory signaling pathways in target cells. This investigation sought to examine whether IL-38 could alleviate DM-induced myocardial injury through the modulation of pyroptosis. Following the induction of type 2 diabetes in mice, IL-38 treatment (with or without NLRP3 overexpression) was administered for an additional 8 weeks. Cardiac function, histological architecture, and cardiomyocyte apoptosis underwent assessment. Levels of pyroptosis-related proteins and associated signaling pathways regulating pyroptosis were evaluated. Additionally, the influence of IL-38 on pyroptosis was examined in cultured primary cardiomyocytes. IL-38 demonstrated protective effects against myocardial damage both in vivo and in vitro. The expression levels of pyroptosis-associated proteins increased in type 2 diabetic mice, while IL-38 administration suppressed the pyroptotic process. Additionally, IL-38 reduced pyroptosis via modulation of the STING/NLRP3 signaling cascade. Nevertheless, enhanced NLRP3 expression or STING pathway stimulation counteracted the beneficial outcomes of IL-38.
