Contribution of Growth Arrest-Specific 5/miR-674 to the Hypothalamus Pituitary Adrenal Axis Regulation Effect by Electroacupuncture following Trauma.

BACKGROUND

Electroacupuncture (EA) can improve trauma-induced hypothalamus pituitary adrenal axis (HPA) hyperactivity. However, the mechanism underlying the EA effect has not been fully understood.

METHODS AND STUDY

DESIGN

This study was undertaken to explore the role of hypothalamic growth arrest-specific 5 (Gas5) in the regulation of EA on HPA axis function post-surgery. Paraventricular nuclear Gas5 levels were upregulated in rats using an intracerebroventricular injection of pAAV-Gas5. Primary hypothalamic neurons and 293T cells were cultured for miRNA and siRNAs detection. Radioimmunoassay, PCR, Western blot, and immunohistochemistry were used for HPA axis function evaluation.

RESULTS

The overexpression of Gas5 abolished the effect of EA on the regulation of trauma-induced HPA axis hyperactivity. Using a bioinformatics analysis and dual luciferase assay, we determined that miRNA-674 was a target of Gas5. Additionally, miRNA-674 levels were found to have decreased in trauma rats, and this effect was reversed after EA intervention. TargetScan analysis showed that serum and glucocorticoid inducible kinase 1 (SGK1) were targets of miR-674. Moreover, we found that SGK1 protein levels increased in trauma rats and SGK1 expression inhibition alleviated HPA axis abnormality post-surgery. EA could improve the number of hypothalamus iba-1 positive cells and hypothalamic interleukin 1 beta protein expression.

CONCLUSIONS

Our study demonstrated the involvement of the hypothalamic Gas5/miRNA-674/SGK1 signaling pathway in EA regulation of HPA axis function after trauma.