Jie Zhang1, Hanchen Liu2, Chenguang Song3, Jinjin Zhang1, Youlei Wang4, Changjun Lv5, Xiaodong Song6. 1. Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China; Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. 2. Department of Medical Oncology, People`s Liberation Army 107th Hospital, Yantai 264003, China. 3. Department of Respiratory Medicine, Zouping Chinese Medicine Hospital, Binzhou 256602, China. 4. Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China. 5. Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China; Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. Electronic address: lucky_lcj@sina.com. 6. Department of Cellular and Genetic Medicine, School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, China; Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou 256602, China. Electronic address: songxd71@163.com.
Abstract
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 antifibrotic activity of astilbin on TGF-β1-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 α-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.
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 antifibrotic activity of astilbin on TGF-β1-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 α-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.