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Tumor necrosis factor superfamily member LIGHT induces epithelial-mesenchymal transition in A549 human alveolar epithelial cells.
Biochem Biophys Res Commun. 2012 Nov 30; 428(4):451-7.BB

Abstract

Fibrosis is an abnormal response to organ injury, characterized by accumulation of activated fibroblasts at the sites of injury. Fibroblasts arise from several sources, including resident fibroblasts and circulating fibrocytes that infiltrate organ tissue. Recently, epithelial-mesenchymal transition (EMT) has been recognized as a source of mesenchymal cells. EMT is induced by various growth factors, such as transforming growth factor (TGF)-β1, and enhanced by inflammatory cytokines. Recently the tumor necrosis factor superfamily member LIGHT has been implicated in the pathogenesis of inflammatory disease and airway remodeling in severe asthma. We hypothesized that LIGHT might contribute to the pathogenesis of airway fibrosis via enhancement of EMT. Therefore, we investigated LIGHT's ability to induce EMT. A549 cells were stimulated with LIGHT, TGF-β1 or both for 48h. To estimate EMT, we evaluated the expression of epithelial and mesenchymal markers using immunocytochemistry, Western blotting and quantitative RT-PCR. Signaling pathways for EMT were characterized by Western analysis to detect phosphorylation of Erk1/2 and smad2. LIGHT enhanced TGF-β1-induced EMT both morphologically, by suppressing E-cadherin and enhancing vimentin, and functionally, by enhancing cell contractility. Additionally, LIGHT induced EMT without TGF-β1. Evaluation of the mechanism showed that LIGHT did not induce TGF-β1 production or affect the smad-snai1 pathway. Inhibition of Erk1/2 phosphorylation reduced LIGHT-induced EMT, indicating the Erk1/2 pathway to be a key pathway in LIGHT-induced EMT. In summary, LIGHT enhanced TGF-β1-induced EMT but also induced EMT via the Erk1/2 pathway by itself, without TGF-β1 signaling. LIGHT may contribute to the pathogenesis of airway fibrosis through enhancement of EMT.

Authors+Show Affiliations

Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23131560

Citation

Mikami, Yu, et al. "Tumor Necrosis Factor Superfamily Member LIGHT Induces Epithelial-mesenchymal Transition in A549 Human Alveolar Epithelial Cells." Biochemical and Biophysical Research Communications, vol. 428, no. 4, 2012, pp. 451-7.
Mikami Y, Yamauchi Y, Horie M, et al. Tumor necrosis factor superfamily member LIGHT induces epithelial-mesenchymal transition in A549 human alveolar epithelial cells. Biochem Biophys Res Commun. 2012;428(4):451-7.
Mikami, Y., Yamauchi, Y., Horie, M., Kase, M., Jo, T., Takizawa, H., Kohyama, T., & Nagase, T. (2012). Tumor necrosis factor superfamily member LIGHT induces epithelial-mesenchymal transition in A549 human alveolar epithelial cells. Biochemical and Biophysical Research Communications, 428(4), 451-7. https://doi.org/10.1016/j.bbrc.2012.10.097
Mikami Y, et al. Tumor Necrosis Factor Superfamily Member LIGHT Induces Epithelial-mesenchymal Transition in A549 Human Alveolar Epithelial Cells. Biochem Biophys Res Commun. 2012 Nov 30;428(4):451-7. PubMed PMID: 23131560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor superfamily member LIGHT induces epithelial-mesenchymal transition in A549 human alveolar epithelial cells. AU - Mikami,Yu, AU - Yamauchi,Yasuhiro, AU - Horie,Masafumi, AU - Kase,Makiko, AU - Jo,Taisuke, AU - Takizawa,Hajime, AU - Kohyama,Tadashi, AU - Nagase,Takahide, Y1 - 2012/11/03/ PY - 2012/09/28/received PY - 2012/10/12/accepted PY - 2012/11/8/entrez PY - 2012/11/8/pubmed PY - 2013/3/27/medline SP - 451 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 428 IS - 4 N2 - Fibrosis is an abnormal response to organ injury, characterized by accumulation of activated fibroblasts at the sites of injury. Fibroblasts arise from several sources, including resident fibroblasts and circulating fibrocytes that infiltrate organ tissue. Recently, epithelial-mesenchymal transition (EMT) has been recognized as a source of mesenchymal cells. EMT is induced by various growth factors, such as transforming growth factor (TGF)-β1, and enhanced by inflammatory cytokines. Recently the tumor necrosis factor superfamily member LIGHT has been implicated in the pathogenesis of inflammatory disease and airway remodeling in severe asthma. We hypothesized that LIGHT might contribute to the pathogenesis of airway fibrosis via enhancement of EMT. Therefore, we investigated LIGHT's ability to induce EMT. A549 cells were stimulated with LIGHT, TGF-β1 or both for 48h. To estimate EMT, we evaluated the expression of epithelial and mesenchymal markers using immunocytochemistry, Western blotting and quantitative RT-PCR. Signaling pathways for EMT were characterized by Western analysis to detect phosphorylation of Erk1/2 and smad2. LIGHT enhanced TGF-β1-induced EMT both morphologically, by suppressing E-cadherin and enhancing vimentin, and functionally, by enhancing cell contractility. Additionally, LIGHT induced EMT without TGF-β1. Evaluation of the mechanism showed that LIGHT did not induce TGF-β1 production or affect the smad-snai1 pathway. Inhibition of Erk1/2 phosphorylation reduced LIGHT-induced EMT, indicating the Erk1/2 pathway to be a key pathway in LIGHT-induced EMT. In summary, LIGHT enhanced TGF-β1-induced EMT but also induced EMT via the Erk1/2 pathway by itself, without TGF-β1 signaling. LIGHT may contribute to the pathogenesis of airway fibrosis through enhancement of EMT. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/23131560/Tumor_necrosis_factor_superfamily_member_LIGHT_induces_epithelial_mesenchymal_transition_in_A549_human_alveolar_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(12)02089-X DB - PRIME DP - Unbound Medicine ER -