Language
English
Publication Date
3-1-2025
Journal
Clinical and Translational Medicine
DOI
10.1002/ctm2.70235
PMID
40008481
PMCID
PMC11862893
PubMedCentral® Posted Date
2-26-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Contrast-induced acute kidney injury (CI-AKI) continues to pose a pressing clinical challenge during invasive cardiovascular procedures due to the limited availability of preventative strategies. We aimed to demonstrate that irisin, a myokine induced by exercise, protects against CI-AKI by inhibiting the cGAS-STING inflammatory pathway.
Methods and results: We explored the relationship between serum irisin levels and CI-AKI incidence in patients administered the contrast media iohexol. Notably, lower serum irisin levels were strongly associated with an increased incidence of CI-AKI following contrast media administration. To establish a causal link between serum irisin levels and CI-AKI, we utilised a mouse model that simulates exercise by overexpressing muscle-specific PGC-1α. This approach showed a significant reduction in tubular injury and mitochondrial dysfunction induced by iohexol via cGAS/STING suppression, thereby diminishing inflammation. Mechanistically, irisin was found to inhibit the activation of cGAS/STING, preventing double stranded DNA (dsDNA) leakage and reducing inflammation in tubular epithelial cells (TECs). Pharmacological inhibition of STING further corroborated these observations. Moreover, we identified integrin complex αV/β5 as the irisin receptor on TECs, which is essential for irisin-mediated suppression of cGAS-STING signalling and resolution of inflammation.
Conclusions: Our data position irisin as a crucial factor in muscle‒kidney crosstalk, inhibiting cGAS-STING signalling and preventing dsDNA leakage via integrin αV/β5 in TECs, thus mitigating tubular injury and inflammation. These data underscore the potential of irisin as both a predictive biomarker for CI-AKI and a promising candidate for preventative strategies against CI-AKI.
Highlights: Irisin mediated muscle-kidney crosstalk mitigated tubular injury and inflammation. Irisin inhibited the cGAS-STING signalling activation via integrin αV/β5 in tubular epithelial cells. Irisin was a predictive biomarker and a promising candidate for CI-AKI.
Keywords
Animals, Acute Kidney Injury, Nucleotidyltransferases, Mice, Fibronectins, Signal Transduction, Contrast Media, Humans, Membrane Proteins, Male, Disease Models, Animal, cGAS‐STING, contrast‐induced acute kidney injury, inflammation, irisin, mPGC‐1α
Published Open-Access
yes
Recommended Citation
Peng, Long; Li, Suhua; Huang, Qiang; et al., "Irisin-Mediated Muscle-Renal Crosstalk as a Protective Mechanism Against Contrast-Induced Acute Kidney Injury via cGAS-Sting Signalling Inhibition" (2025). Faculty and Staff Publications. 4730.
https://digitalcommons.library.tmc.edu/baylor_docs/4730