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p38 MAPK is Crucial for Wnt1- and LiCl-Induced Epithelial Mesenchymal Transition

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Summary

Idiopathic pulmonary fibrosis (IPF) is characterized by myofibroblast foci in lung parenchyma. Myofibroblasts are thought to originate from epithelial-to-mesenchymal transition (EMT). Wnt1 and lithium chloride (LiCl) induce EMT in alveolar epithelial cells (AECs), but the mechanisms are unclear. AECs were treated with Wnt1 and LiCl, respectively; morphological change and molecular changes of EMT, including E-cadherin, fibronectin, and vimentin, were observed. SB203580 was administrated to test the role of p38 МАРК signaling in EMT. Then AECs were treated with siRNAs targeting p38 МАРК to further test the effects of p38 МАРК, and the role was further confirmed by re-expression of p38 МАРК. At last P-catenin siRNA was used to test the role of β-catenin in the EMT process and relationship of β-catenin and p38 МАРК was concluded. Exposure of AECs to Wnt1 and LiCl resulted in upregulation of vimentin and fibronectin with subsequent downregulation of E-cadherin. Wnt1 and LiCl stimulated the p38 МАРК signaling pathways. Perturbing the p38 МАРК pathway either by SB203580 or through p38 МАРК siRNA blocked EMT and inhibited fibronetin synthesis, which were reversed by transfection of p38 МАРК expression plasmid. β-catenin siRNA attenuated the EMT process and decreased p38 МАРК phosphorylation, indicating that β-catenin is involved in the EMTrelated changes through regulation of p38 МАРК phosphorylation. These findings suggest that p38 МАРК participates in the pathogenesis of EMT through Wnt pathway and that p38 МАРК may be a novel target for IPF therapy.

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  1. These authors contributed equally to this study.

Authors and Affiliations

  1. Department of Pulmonary Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Chun-xiao Fang, Xi-ming Wang, Na Zhang, Ji-na Ma, Tai-hua Wu, Zhong-he Zhang, Guang-dong Zhao & Ya-dong Zhao

  2. Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Chun-mei Ma

  3. Department of Pulmonary Medicine, Dalian Central Hospital Affiliated to Dalian Medical University, Dalian, 116033, China

    Ling Jiang

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  1. Chun-xiao Fang
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Fang, Cx., Ma, Cm., Jiang, L. et al. p38 MAPK is Crucial for Wnt1- and LiCl-Induced Epithelial Mesenchymal Transition. CURR MED SCI 38, 473–481 (2018). https://doi.org/10.1007/s11596-018-1903-4

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  • DOI: https://doi.org/10.1007/s11596-018-1903-4

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