HIF‐1α regulates EMT via the Snail and β‐catenin pathways in paraquat poisoning‐induced early pulmonary fibrosis

Journal of Cellular and Molecular Medicine - Tập 20 Số 4 - Trang 688-697 - 2016
Yong Zhu1, Jiuting Tan1, Hui Xie1, Jinfeng Wang1, Xiaoxiao Meng1, Ruilan Wang1
1Department of Critical Care Medicine, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

Tóm tắt

AbstractParaquat (PQ) poisoning‐induced pulmonary fibrosis is one of the primary causes of death in patients with PQ poisoning. Hypoxia‐inducible factor‐1α (HIF‐1α) and epithelial‐mesenchymal transition (EMT) are involved in the progression of pulmonary fibrosis. Snail and β‐catenin are two other factors involved in promoting EMT. However, the relationship among HIF‐1α, Snail and β‐catenin in PQ poisoning‐induced pulmonary fibrosis is not clear. Our research aimed to determine whether the regulation of HIF‐1α in EMT occurs via the Snail and β‐catenin pathways in PQ poisoning‐induced pulmonary fibrosis. Sixty‐six Sprague–Dawley rats were randomly and evenly divided into a control group and a PQ group. The PQ group was treated with an intragastric infusion of a 20% PQ solution (50 mg/kg) for 2, 6, 12, 24, 48 and 72 hrs. A549 and RLE‐6TN cell lines were transfected with HIF‐1α siRNA for 48 hrs before being exposed to PQ. Western blotting, real‐time quantitative PCR, immunofluorescence, immunohistochemistry and other assays were used in our research. In vivo, the protein levels of HIF‐1α and α‐SMA were increased at 2 hrs and the level of ZO‐1 (Zonula Occluden‐1) was reduced at 12 hrs. In vitro, the transient transfection of HIF‐1α siRNA resulted in a decrease in the degree of EMT. The expression levels of Snail and β‐catenin were significantly reduced when HIF‐α was silenced. These data demonstrate that EMT may be involved in PQ poisoning‐induced pulmonary fibrosis and regulated by HIF‐1α via the Snail and β‐catenin pathways. Hypoxia‐inducible factor‐1α may be a therapeutic target for the treatment of PQ poisoning‐induced pulmonary fibrosis.

Từ khóa


Tài liệu tham khảo

10.3346/jkms.2014.29.11.1441

Zhang BL, 2010, Literature analysis of paraquat poisoning in China (1991–2008), Chin J Crit Care Med, 30, 139

10.1192/bjp.bp.105.020834

Sittipunt C, 2005, Paraquat poisoning, Respir Care, 50, 383

10.1080/10408440701669959

10.2217/imt.12.122

10.1038/jid.2011.141

10.1038/nrrheum.2011.205

10.1038/onc.2012.510

10.1007/s00109-015-1289-8

10.1038/nm.2807

10.1016/j.cell.2009.11.007

10.1152/ajplung.00007.2009

Wang RL, 2012, The relationship between HIF‐1alpha expression and the early lung fibrosis in rats with acute paraquat poisoning, Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 30, 273

10.1038/nrc2131

10.1038/sj.onc.1205416

10.1242/jcs.01004

10.1172/JCI74159

10.1038/nrm2717

10.5173/ceju.2012.03.art4

10.1146/annurev.cellbio.19.011102.111135

10.1016/j.tcb.2005.03.002

10.1016/j.gde.2005.12.007

10.1126/scisignal.2005189

10.1038/nature04871

10.1177/1535370213498978

10.1016/S1043-6618(02)00122-6

10.1007/s004140050233

10.1172/JCI39104

10.1091/mbc.E14-01-0044

10.1158/1078-0432.CCR-10-1360

10.1016/S0002-9440(10)63501-8

10.1038/ncb1691

10.1158/0008-5472.CAN-05-3719

10.1016/j.bbamcr.2013.02.029

10.1016/j.canlet.2013.04.024

10.1056/NEJMra1300575

10.3181/0707-MR-190

10.1146/annurev-physiol-012110-142225

10.1073/pnas.0605669103

10.1016/S0002-9440(10)62351-6

10.1006/excr.1998.4172

10.1111/jcmm.12506

10.1183/09031936.00015612

10.1126/scitranslmed.3001510

10.1038/sj.onc.1208927

Higgins DF, 2007, Hypoxia promotes fibrogenesis in vivo via HIF‐1 stimulation of epithelial‐to‐mesenchymal transition, J Clin Invest, 117, 3810

10.4161/cc.7.9.5804

10.1242/dev.01907

10.1242/jcs.068692

10.1038/nrm3758

10.1038/nrc3419

10.1101/cshperspect.a002915

10.1172/JCI36183

10.1681/ASN.2009121236

10.1681/ASN.2009010019

10.1074/jbc.M115.636944

10.1186/1471-2407-13-108

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Thông tin xuất bản

Journal of Cellular and Molecular Medicine

Tập 20 Số 4

688-697

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