Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 DOI: 10.1159/000489367 © 2018 The Author(s) www.karger.com/cpb online:April April30,30, 2018 Published online: 2018 Published by S. Karger AG, Basel and Biochemistry Published www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium Accepted: February 08, 2018
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution IRUFRPPHUFLDOSXUSRVHVDVZHOODVDQ\GLVWULEXWLRQRIPRGLÀHGPDWHULDOUHTXLUHVZULWWHQSHUPLVVLRQ
Original Paper
Histone Deacetylases Promote ER Stress Induced Epithelial Mesenchymal Transition in Human Lung Epithelial Cells Daishun Liu Honglan Zhu Guichuan Huang
Ling Gong
Shenglan Pu
Yang Wu
Wei Zhang
'HSDUWPHQWRI5HVSLUDWRU\0HGLFLQH7KH)LUVW3HRSOH·V+RVSLWDORI=XQ\L7KH7KLUG$IÀOLDWHG+RVSLWDO of Zunyi Medical College, Institute of Respiratory Diseases in Zunyi, Zunyi, Guizhou, China
Key Words Histone deacetylase • Endoplasmic reticulum stress • Epithelial–mesenchymal transition • 3XOPRQDU\ÀEURVLV Abstract Background/Aims: Epithelial to mesenchymal transition (EMT) is a crucial process involved LQSXOPRQDU\ÀEURVLV7KLVVWXG\DLPHGWRH[SORUHWKHUROHRIKLVWRQHGHDFHW\ODVHV+'$&V and endoplasmic reticulum (ER) stress in EMT in human lung epithelial cells. Methods: Human lung adenocarcinoma A549 cells were treated with bleomycin and tunicamycin to induce EMT. 7KHSUROLIHUDWLRQRI$FHOOVZDVGHWHFWHGE\077DVVD\7KHH[SUHVVLRQRI+'$&VDQG(07 PDUNHUVZDVGHWHFWHGE\3&5DQG:HVWHUQEORWDQDO\VLV7KHVHFUHWLRQRI7*)DŽDQGFROODJHQ ,ZDVH[DPLQHGE\(/,6$Results: A549 cells switched from a cobblestone-like appearance WR DQ HORQJDWHG ÀEUREODVW OLNH DSSHDUDQFH DIWHU H[SRVXUH WR WXQLFDP\FLQ RU EOHRP\FLQ DFFRPSDQLHG E\ LQFUHDVHG H[SUHVVLRQ RI 1FDGKHULQ į60$ DQG &ROODJHQ , 0HDQZKLOH *53ZDVXSUHJXODWHGLQ$FHOOVH[SRVHGWRWXQLFDP\FLQRUEOHRP\FLQ7KHVHFKDQJHV induced by tunicamycin or bleomycin could be abrogated by 4-PBA. Moreover, tunicamycin DQGEOHRP\FLQSURPRWHGWKHH[SUHVVLRQRI+'$&DQG+'$&DQG+'$&VLQKLELWRU6$+$ abrogated the morphological and biochemical changes in A549 cells. 4-PBA and SAHA LQKLELWHGWKHXSUHJXODWLRQRISXOPRQDU\ÀEURVLVIDFWRUV7*)DŽDQG,/DQGWKHDFWLYDWLRQ of Smad pathway induced by tunicamycin or bleomycin. Conclusions: :HSURYLGHWKHÀUVW evidence that tunicamycin and bleomycin induce ER stress and EMT in lung epithelial cells via the upregulation of HDACs. HDACs inhibitor could inhibit ER stress induced upregulation RI SXOPRQDU\ ÀEURVLV IDFWRUV DQG WKH DFWLYDWLRQ RI 6PDG SDWKZD\ +'$&V LQKLELWRUV DUH SURPLVLQJDJHQWVIRUWKHWKHUDS\RISXOPRQDU\ÀEURVLV © 2018 The Author(s) Published by S. Karger AG, Basel
Introduction
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ǡ͵ǦͶǡ Daishun Liu
Department of Respiratory Medicine, The First People’s Hospital of Zunyi, Zunyi, Guizhou (China) E-Mail
[email protected]
1821
Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
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ϐǤ Materials and Methods Cell culture and treatment
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
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Results
Tunicamycin and bleomycin induce EMT of A549 cells ϐ
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
Fig. 1.
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Ǥ Tunicamycin and bleomycin induce ER stress in A549 cells
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
Fig. 3.
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Tunicamycin and bleomycin upregulate HDACs in A549 cells
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
Tunicamycin and bleomycin induce ER stress by upregulating HDACs
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
Fig. 5.
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
Fig. 6.
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
ǦȾͳ Ǧ͵ʹ
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
Fig. 8.
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ϐǤ Conclusion
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ǡ ϐǤ Acknowledgements
ȋǤ ʹͲͳͶǦͳǦͲͶȌǡ
ȋǤ ʹͲͳͷǦͳǦͲͳȌ
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ʹͲͳͷǦͶͲͳͺȌǤ Disclosure Statement
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Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
References ͳ
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ϐǤ ʹͲͲǢʹǣͳ͵ǦͳͶʹǤ ǡǦ ǡǡǣ
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ϐǣǤʹͲͳ͵ǢʹʹǣʹͺͳǦʹͻͳǤ ǡ ǡǣ
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1833
Physiol Biochem 2018;46:1821-1834 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000489367 and Biochemistry Published online: April 30, 2018 www.karger.com/cpb Liu et al.: HDACs Promotes EMT of Lung Epithelium
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1834