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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

miR-205 Suppresses Pulmonary Fibrosis by Targeting GATA3 Through Inhibition of Endoplasmic Reticulum Stress

Author(s): Bingke Sun, Shumin Xu, Yanli Yan, Yusheng Li, Hongqiang Li, Guizhen Zheng, Tiancao Dong and Jianwen Bai*

Volume 21, Issue 8, 2020

Page: [720 - 726] Pages: 7

DOI: 10.2174/1389201021666191210115614

Price: $65

Abstract

Objective: To investigate the role of miR-205 and GATA3 in Pulmonary Fibrosis (PF).

Methods: Bleomycin (BLM) was used to induce PF in SD rats and in vitro PF model was established by using TGFβ1-induced RLE-6TN cells. miR-205 mimics were used for the overexpression of miR- 205. The expression of miR-205, GATA3, α-SMA, Collagen I, CHOP and GRP78 were measured using RT-qPCR or western blotting. Dual-luciferase reporter assay was used to confirm binding between GATA3 3’-UTR and miR-205.

Results: The expression of miR-205 was significantly down-regulated, while the expression of GATA3 was remarkably up-regulated in the model rats. GATA3 levels were remarkably decreased when miR-205 was overexpressed. When miR-205 was overexpressed, the lung injury by BLM-induced fibrosis was improved. The expression of α-SMA, Collagen I, as well as GRP78 and CHOP, was significantly up-regulated in both in vivo and in vitro PF models, and overexpression of miR-205 remarkably reversed the effects. Dual-luciferase reporter assay showed that miR-205 directly targeted and negatively regulated GATA3.

Conclusion: miR-205 improved pulmonary fibrosis through inhibiting ER-stress by targeting GATA3.

Keywords: miR-205, pulmonary fibrosis, GATA3, CHOP, endoplasmic reticulum stress, alveolar epithelial cells.

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[1]
Martinez, F.J.; Chisholm, A.; Collard, H.R.; Flaherty, K.R.; Myers, J.; Raghu, G.; Walsh, S.L.; White, E.S.; Richeldi, L. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Respir. Med., 2017, 5(1), 61-71.
[http://dx.doi.org/10.1016/S2213-2600(16)30325-3] [PMID: 27932290]
[2]
Raghu, G.; Collard, H.R.; Egan, J.J.; Martinez, F.J.; Behr, J.; Brown, K.K.; Colby, T.V.; Cordier, J.F.; Flaherty, K.R.; Lasky, J.A.; Lynch, D.A.; Ryu, J.H.; Swigris, J.J.; Wells, A.U.; Ancochea, J.; Bouros, D.; Carvalho, C.; Costabel, U.; Ebina, M.; Hansell, D.M.; Johkoh, T.; Kim, D.S.; King, T.E., Jr; Kondoh, Y.; Myers, J.; Müller, N.L.; Nicholson, A.G.; Richeldi, L.; Selman, M.; Dudden, R.F.; Griss, B.S.; Protzko, S.L.; Schünemann, H.J. ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. Am. J. Respir. Crit. Care Med., 2011, 183(6), 788-824.
[http://dx.doi.org/10.1164/rccm.2009-040GL] [PMID: 21471066]
[3]
Sgalla, G.; Iovene, B.; Calvello, M.; Ori, M.; Varone, F.; Richeldi, L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir. Res., 2018, 19(1), 32.
[http://dx.doi.org/10.1186/s12931-018-0730-2] [PMID: 29471816]
[4]
Guan, S.; Zhou, J. Frizzled-7 mediates TGF-β-induced pulmonary fibrosis by transmitting non-canonical Wnt signaling. Exp. Cell Res., 2017, 359(1), 226-234.
[http://dx.doi.org/10.1016/j.yexcr.2017.07.025] [PMID: 28736081]
[5]
Tanjore, H.; Blackwell, T.S.; Lawson, W.E. Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol., 2012, 302(8), L721-L729.
[http://dx.doi.org/10.1152/ajplung.00410.2011] [PMID: 22287606]
[6]
Steele, M.P.; Schwartz, D.A. Molecular mechanisms in progressive idiopathic pulmonary fibrosis. Annu. Rev. Med., 2013, 64(1), 265-276.
[http://dx.doi.org/10.1146/annurev-med-042711-142004] [PMID: 23020878]
[7]
Bueno, M.; Lai, Y.C.; Romero, Y.; Brands, J.; St Croix, C.M.; Kamga, C.; Corey, C.; Herazo-Maya, J.D.; Sembrat, J.; Lee, J.S.; Duncan, S.R.; Rojas, M.; Shiva, S.; Chu, C.T.; Mora, A.L. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J. Clin. Invest., 2015, 125(2), 521-538.
[http://dx.doi.org/10.1172/JCI74942] [PMID: 25562319]
[8]
Dickens, J.A.; Malzer, E.; Chambers, J.E. Pulmonary endoplasmic reticulum stress:Scars, smoke, and suffocation. Febs J., 2018, 286(2), 322-341.
[http://dx.doi.org/10.1111/febs.14381] [PMID: 29323786]
[9]
Wang, Y.C.; Dong, J.; Nie, J.; Zhu, J.X.; Wang, H.; Chen, Q.; Chen, J.Y.; Xia, J.M.; Shuai, W. Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition. Apoptosis, 2017, 22(9), 1147-1156.
[http://dx.doi.org/10.1007/s10495-017-1393-z] [PMID: 28677092]
[10]
Li, N.; Long, B.; Han, W.; Yuan, S.; Wang, K. microRNAs: important regulators of stem cells. Stem Cell Res. Ther., 2017, 8(1), 110.
[http://dx.doi.org/10.1186/s13287-017-0551-0] [PMID: 28494789]
[11]
Pandit, K.V.; Milosevic, J.; Kaminski, N. MicroRNAs in idiopathic pulmonary fibrosis. Transl. Res., 2011, 157(4), 191-199.
[http://dx.doi.org/10.1016/j.trsl.2011.01.012] [PMID: 21420029]
[12]
Xie, T.; Liang, J.; Guo, R.; Liu, N.; Noble, P.W.; Jiang, D. Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis identifies multiple sites of molecular regulation. Physiol. Genomics, 2011, 43(9), 479-487.
[http://dx.doi.org/10.1152/physiolgenomics.00222.2010] [PMID: 21266501]
[13]
Rajasekaran, S.; Rajaguru, P.; Sudhakar Gandhi, P.S. MicroRNAs as potential targets for progressive pulmonary fibrosis. Front. Pharmacol., 2015, 6(53), 254.
[http://dx.doi.org/10.3389/fphar.2015.00254] [PMID: 26594173]
[14]
Eyking, A.; Reis, H.; Frank, M.; Gerken, G.; Schmid, K.W.; Cario, E. MiR-205 and MiR-373 are associated with aggressive human mucinous colorectal cancer. PLoS One, 2016, 11(6)e0156871
[http://dx.doi.org/10.1371/journal.pone.0156871] [PMID: 27271572]
[15]
Huo, L.; Wang, Y.; Gong, Y.; Krishnamurthy, S.; Wang, J.; Diao, L.; Liu, C.G.; Liu, X.; Lin, F.; Symmans, W.F.; Wei, W.; Zhang, X.; Sun, L.; Alvarez, R.H.; Ueno, N.T.; Fouad, T.M.; Harano, K.; Debeb, B.G.; Wu, Y.; Reuben, J.; Cristofanilli, M.; Zuo, Z. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer. Mod. Pathol., 2016, 29(4), 330-346.
[http://dx.doi.org/10.1038/modpathol.2016.38] [PMID: 26916073]
[16]
Muratsu-Ikeda, S.; Nangaku, M.; Ikeda, Y.; Tanaka, T.; Wada, T.; Inagi, R. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells. PLoS One, 2012, 7(7)e41462
[http://dx.doi.org/10.1371/journal.pone.0041462] [PMID: 22859986]
[17]
Terzic, T.; Mills, A.M.; Zadeh, S. GATA3 expression in common gynecologic carcinomas: A potential pitfall. Int. J. Gynecol. Pathol., 2019, 38(5), 485-492.
[http://dx.doi.org/10.1097/PGP.0000000000000541] [PMID: 30059453]
[18]
Hercor, M.; Anciaux, M.; Denanglaire, S.; Debuisson, D.; Leo, O.; Andris, F. Antigen-presenting cell-derived IL-6 restricts the expression of GATA3 and IL-4 by follicular helper T cells. J. Leukoc. Biol., 2017, 101(1), 5-14.
[http://dx.doi.org/10.1189/jlb.1HI1115-511R] [PMID: 27474166]
[19]
Tjarks, B.J.; Pownell, B.R.; Evans, C.; Thompson, P.A.; Kerkvliet, A.M.; Koch, M.R.D.; Jassim, A.D. Evaluation and comparison of staining patterns of factor XIIIa (AC-1A1), adipophilin and GATA3 in sebaceous neoplasia. J. Cutan. Pathol., 2018, 45(1), 1-7.
[http://dx.doi.org/10.1111/cup.13037] [PMID: 28873247]
[20]
Kimura, T.; Ishii, Y.; Yoh, K.; Morishima, Y.; Iizuka, T.; Kiwamoto, T.; Matsuno, Y.; Homma, S.; Nomura, A.; Sakamoto, T.; Takahashi, S.; Sekizawa, K. Overexpression of the transcription factor GATA-3 enhances the development of pulmonary fibrosis. Am. J. Pathol., 2006, 169(1), 96-104.
[http://dx.doi.org/10.2353/ajpath.2006.051160] [PMID: 16816364]
[21]
Zhao, J.; Zang, J.; Lin, Y. Polyphenol-rich blue honeysuckle extract alleviates silica-induced lung fibrosis by modulating Th immune response and NRF2/HO-1 MAPK signaling. J. Funct. Foods, 2019..
[http://dx.doi.org/10.1016/j.jff.2018.12.030]
[22]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[23]
Cao, Y.; Liu, Y.; Ping, F. miR-200b/c attenuates lipopolysaccharide-induced early pulmonary fibrosis by targeting ZEB1/2 via p38 MAPK and TGF-β/smad3 signaling pathways. Lab. Invest., 2017.
[PMID: 29200203]
[24]
Bodempudi, V.; Hergert, P.; Smith, K.; Xia, H.; Herrera, J.; Peterson, M.; Khalil, W.; Kahm, J.; Bitterman, P.B.; Henke, C.A. miR-210 promotes IPF fibroblast proliferation in response to hypoxia. Am. J. Physiol. Lung Cell. Mol. Physiol., 2014, 307(4), L283-L294.
[http://dx.doi.org/10.1152/ajplung.00069.2014] [PMID: 24951777]
[25]
Cai, J.; Fang, L.; Huang, Y.; Li, R.; Yuan, J.; Yang, Y.; Zhu, X.; Chen, B.; Wu, J.; Li, M. miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant phenotypes in non-small cell lung cancer. Cancer Res., 2013, 73(17), 5402-5415.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0297] [PMID: 23856247]
[26]
Liang, S.; Cai, G.Y.; Duan, Z.Y.; Liu, S.W.; Wu, J.; Lv, Y.; Hou, K.; Li, Z.X.; Zhang, X.G.; Chen, X.M. Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy. BMC Nephrol., 2017, 18(1), 63.
[http://dx.doi.org/10.1186/s12882-017-0482-0] [PMID: 28201996]
[27]
Yoh, K.; Ojima, M.; Takahashi, S. Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic mice. Exp. Anim., 2015, 64(4), 353-362.
[http://dx.doi.org/10.1538/expanim.15-0019] [PMID: 26156402]

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