Tanshinone IIA ameliorates the bleomycin-induced endothelial-to-mesenchymal transition via the Akt/mTOR/p70S6K pathway in a murine model of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune inflammatory and vascular disorder leading to progressive tissue fibrosis. Tanshinone IIA (Tan IIA) is a phytochemical extracted from the Chinese herb Salvia miltiorrhiza that exhibits diverse activities. In this study, we attempted to evaluate the potential impact of Tan IIA on the skin fibrosis-related endothelial-to-mesenchymal transition (EndoMT) and investigate the underlying molecular mechanisms. EndoMT-related indexes including morphological characteristics, functional changes, histological parameters, expression levels of extracellular matrix associated genes, and changes in the expression of related biomarkers in dermal fibrosis were assessed. Tan IIA had a strong anti-fibrotic effect through amelioration of skin thickness and collagen deposition. Moreover, Tan IIA partially reversed bleomycin-induced EndoMT both in vivo and in vitro. Additionally, Tan IIA mitigated the diminution of tube formation in endothelial cells induced by bleomycin. Furthermore, mechanistically, the activation of the Akt/mTOR/p70S6K pathway was found to be involved in bleomycin-treated SSc mouse model, which was alleviated by Tan IIA. In summary, these data suggest that Tan IIA alleviates SSc-related dermal fibrosis and EndoMT and that the Akt/mTOR/p70S6K signaling pathway is involved in this regulation, thus supporting the potential of Tan IIA as a disease-modifying candidate agent for treating the vascular damage of SSc.