Mechanism of Tripchlorolide Inhibiting Hedgehog Signaling Pathway to Delay Lung Fibrosis

Abstract

Background: The paper aimed to determine whether Tripchlorolide can exert anti-fibrotic effects by up-regulating Sufu to influence the Hedgehog signaling pathway, and to promote the application of Tripchlorolide in diseases associated with the Hedgehog signaling pathway. Material and Methods: In vivo experiment, bronchoalveolar lavage was performed on the 7th day after intratracheal instillation of bleomycin. The number of inflammatory cells and IL-6 levels were analyzed to observe the anti-inflammatory effect of Tripchlorolide. The lung tissues were obtained on the 14th day. The lung tissue injury was observed, and the expressions of a-SMA, collagen I, TGF-β i, Gli 1 and Sufu were determined. In vitro experiments, mouse lung was transfected with lentivirus to make fibroblasts. The Sufii was overexpressed, the changes in Gli 1 and Gli 2 levels were observed. The effects of the overexpressed Sufti of on the phenotype transformed a-SMA and collagen I levels in TGF-β 1 induced mouse lung fibroblasts were observed. Results: After administration with bleomycin, IL-6 level, total number of cells, neutrophils and macrophages in BALF of the Tripchlorolide group mice were reduced. The lung injury score, the expressions of lung tissue TGF-βl, a-SMA and Collagen I were low. The expression of Sufu was high, while the expression of Gli 1 was low. Compared with the groups in which cells were not transfected with lentivirus, the expression of Sufu in the transfected cells increased, and the expressions of Gli 1 and Gli 2 decreased. After stimulation with TGF-β Sufu decreased. Conclusion: Tripchlorolide can inhibit Hedgehog signaling pathway by up-regulating Sufu to exert an anti-fibrotic effect.