STAT6/VDR Axis Mitigates Lung Inflammatory Injury by Promoting Nrf2 Signaling Pathway
Youjing Yang1, Qianmin Li1, Shuhui Wei1
1School of Public Health, Medical College of Soochow University, 199 Ren'ai Road, Suzhou 215123, China.
Oxidative Medicine and Cellular Longevity
|January 20, 2022
Summary
Signal transducer and activator of transcription 6 (STAT6) activation protects against lung inflammatory injury by enhancing antioxidant capacity. STAT6 promotes Vitamin D receptor (VDR) nuclear translocation, activating the Nrf2 pathway and protecting against oxidative stress.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Lung inflammatory injury is a significant global health issue, involving inflammatory cell infiltration, pulmonary septum thickening, and epithelial cell oxidative stress.
- Signal transducer and activator of transcription 6 (STAT6) is a key immune response regulator, but its role in tissue inflammatory injury requires further elucidation.
Purpose of the Study:
- To investigate the protective role of STAT6 activation against particle-induced lung inflammatory injury.
- To elucidate the underlying molecular mechanisms involving oxidative stress, Nrf2 signaling, and Vitamin D receptor (VDR) interactions.
Main Methods:
- Studied particle-induced lung injury in the context of STAT6 activation and genetic ablation.
- Assessed lung antioxidant capacity by measuring malondialdehyde and glutathione levels and analyzing the Nrf2 signaling pathway.
- Utilized human bronchial epithelial cells (BEAS-2B) to examine the effects of VDR silencing on STAT6-mediated Nrf2 activation and autophagy.
Main Results:
- Genetic ablation of STAT6 exacerbated particle-induced lung injury, primarily by impairing antioxidant capacity through Nrf2 pathway downregulation.
- Silencing VDR in bronchial epithelial cells suppressed autophagy-mediated Nrf2 activation, worsening cell damage.
- STAT6 activation facilitated VDR nuclear translocation, enhancing autophagy-related gene transcription and inducing Nrf2 signaling, effects abolished by VDR silencing.
Conclusions:
- STAT6 activation confers protection against particle-induced lung inflammatory injury by bolstering the lung's antioxidant defense mechanisms.
- The mechanism involves STAT6-mediated promotion of VDR nuclear translocation, which subsequently activates the Nrf2 pathway via autophagy.
- These findings highlight STAT6's critical role in mitigating oxidative damage and suggest its potential as a therapeutic target for inflammatory respiratory diseases.
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