IL-32 induces epithelial-mesenchymal transition by triggering endoplasmic reticulum stress in A549 cells
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RESEARCH ARTICLE
Open Access
IL-32 induces epithelial-mesenchymal transition by triggering endoplasmic reticulum stress in A549 cells Ling Gong1,2†, Gang Liu2,3†, Honglan Zhu2, Caihong Li4, Pengmei Li4, Changlu Liu4, Hongbo Tang2, Kaifeng Wu2,5, Jie Wu2,5, Daishun Liu2,6* and Xiaoping Tang1*
Abstract Background: Epithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF. Methods: Human lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting. Results: Stimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, Vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA. Conclusions: These results suggest that IL-32 induces EMT in A549 cells by triggering ER stress, and IL-32 may be a novel marker for IPF. Keywords: Idiopathic pulmonary fibrosis, Epithelial-mesenchymal transition, Endoplasmic reticulum stress, IL-32
* Correspondence: [email protected]; [email protected] † Ling Gong and Gang Liu contributed equally to this work. 2 Department of Respiratory Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi 563000, Guizhou, China 1 The First Clinical Medical College, Jinan University, 601 W. Huangpu Avenue, Guangzhou 510630, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by
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