Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway

作者:Zhang, Jie; Liu, Hanchen; Song, Chenguang; Zhang, Jinjin; Wang, Youlei; Lv, Changjun*; Song, Xiaodong*
来源:Pulmonary Pharmacology & Therapeutics, 2018, 50: 19-27.
DOI:10.1016/j.pupt.2018.03.006

摘要

Background and objective: The nature of pulmonary fibrosis involves inadequate repair of the epithelial cell barrier accompanied by impaired regulation of the fibroblast. Moreover, pulmonary fibrosis currently lacks an effective therapeutic drug. This study targets the protection of the epithelial cell and fibroblast to identify a novel, potentially therapeutic drug (i.e., astilbin). Methods: In this study, the cytotoxicity of astilbin was firstly detected using CCK-8. A real-time proliferation/migration analysis system was used to test the inhibitory proliferation and migration of astilbin in vitro. The expression of mesenchymal markers and the loss of epithelial cell markers were analyzed to evaluate the anti fibrotic activity of astilbin on TGF-beta 1-treated AEC-II and L929 cells and bleomycin-treated mice. Then, in fibrosis-associated signaling pathways, the regulation of astilbin was tested using RNA sequencing and Cignal Finder 45-Pathway system. Rescue and other experiments were used to confirm this pathway regulation further. Results: The data showed that astilbin inhibited proliferation and migration of cell samples. Its treatment resulted in the reduction of pathological score and collagen deposition, with a decrease in alpha-SMA and Snail and an increase in E-cadherin and SP-C in vivo and in vitro. The fibrosis-associated aberrant genes are some of the most notable components of the Hedgehog signaling pathway. Conclusions: Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway and has potential therapeutic value for lung fibrosis treatment.