title: MiR-338* targeting smoothened to inhibit pulmonary fibrosis by epithelial-mesenchymal transition.
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease involving pulmonary injury associated with tissue repair, dysfunction and fibrosis. Recent studies indicate that some microRNAs (miRNAs) may play critical roles in the pathogenesis of pulmonary fibrosis. In this study, we aim to investigate whether miR-338* (miR-338-5p), which has been found to be associated with tumor progression, is associated with pathological process of pulmonary fibrosis. Balb/c mice were treated with bleomycin (BLM) to establish IPF models. Targtscan was used to predict the downstream target of miR-338*. Morphological changes were observed with light microscope and epithelial to mesenchymal transition (EMT) markers were detected by western blot. The expression of miR-338* or downstream target SMO was analyzed by real-time quantitative RT-PCR, northern blot or western blot. MiR-338* was down-regulated in the lung tissue from mice with bleomycin-induced pulmonary fibrosis. The smoothened (SMO) is a direct target of miR-338*, and knocking-down the expression of SMO could partially rescue the fibrotic phenotype of TGF-β-induced NuLi-1 cells. Over-expression of SMO led to the fibrotic phenotype of NuLi-1 cells even without TGF-β treatment. These findings showed that the over-expression of SMO contributed to the fibrotic phenotype of NuLi-1 cells by affecting the epithelial-to-mesenchymal transition (EMT) procedure. Furthermore, in vivo, lentivirus-mediated over-expression of miR-338* can alleviate lung fibrosis induced by bleomycin in mice. In conclusion, our results suggest that miR-338* can target SMO to reduce the EMT procedure and thus postpone the development of pulmonary fibrosis.
authors: Department of Medical Genetics, Nanjing University School of MedicineNanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of MedicineNanjing, China; Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing, China.
authors: Yi
authors: Y
authors: Zhuang
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Jinghong
authors: J
authors: Dai
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Yongsheng
authors: Y
authors: Wang
authors: Department of Medical Genetics, Nanjing University School of MedicineNanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of MedicineNanjing, China.
authors: Huan
authors: H
authors: Zhang
authors: Department of Medical Genetics, Nanjing University School of MedicineNanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of MedicineNanjing, China.
authors: Xinxiu
authors: X
authors: Li
authors: Department of Medical Genetics, Nanjing University School of MedicineNanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of MedicineNanjing, China.
authors: Chunli
authors: C
authors: Wang
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Mengshu
authors: M
authors: Cao
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Yin
authors: Y
authors: Liu
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Jingjing
authors: J
authors: Ding
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Hourong
authors: H
authors: Cai
authors: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing, China.
authors: Deping
authors: D
authors: Zhang
authors: Department of Medical Genetics, Nanjing University School of MedicineNanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of MedicineNanjing, China.
authors: Yaping
authors: Y
authors: Wang
keywords: EMT; Idiopathic pulmonary fibrosis; SMO; miR-338-5p; pathogenesis