Si-Miao-Yong-An decoction alleviates thromboangiitis obliterans by regulating miR-548j-5p/IL-17A signaling pathway

Thromboangiitis obliterans (TAO) is a rare chronic, progressive, and segmental inflammatory disease, but has a high rate on amputation, that severely hazard to patient's quality of life. Si-Miao-Yong-An decoction (SMYA), a traditional prescription, possesses the efficacy of anti-inflammatory, anti-thrombotic and other pharmacological activities. Clinically, it was fully proved to be effective for TAO therapy, but the specific therapeutic effect of SMYA on TAO has been unknown. Thus, deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely important. In this work, we found the elevated IL-17A level in peripheral blood mononuclear cells of TAO patients, while miR-548j-5p expression was significantly reduced. Simultaneously, it presented a negatively correlated between levels of miR-548j-5p and IL-17A. In vitro experiments indicated that over-expressed miR-548j-5p induced the reduction in IL-17A level. However, down-regulated miR-548j-5p exhibited the inverse trend. Using dual luciferase assay, we further affirmed that miR-548j-5p was target to IL-17A. Moreover, SMYA-containing serum effectively led to a decrease in IL-17A level through a rise in expression of miR-548j-5p. More importantly, the results of In vivo tests suggested that SMYA alleviated the formation of TAO rely on IL-17A inhibited by increasing miR-548j-5p expression in vascular tissues. Conclusionly, SMYA can markedly raise the expression miR-548j-5p level, thereby reducing the target gene IL-17A level, thus alleviating the occurrence of TAO. And the pathogenesis of TAO was further elucidated through the perspective of epigenetic immune regulation, which involved in the SMYA/miR-548j-5p/IL-17A information axis. Our research not only provides new targets and pathways for clinical diagnosis and treatment of TAO, but also promotes innovation in traditional Chinese medicine.