HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis.
HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis.
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DOI：
10.1111/jcmm.12769
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发表时间：
2016-04
影响因子：
5.3
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Zhu Y;Tan J;Xie H;Wang J;Meng X;Wang R
百草枯（PQ）中毒引起的肺纤维化是PQ中毒患者死亡的主要原因之一。缺氧诱导因子- 1α (HIF - 1α)和上皮-间充质转化（EMT）参与肺纤维化的进展。Snail和β -连环蛋白是促进EMT的另外两个因子。然而，HIF - 1α、Snail和β - catenin在PQ中毒诱导的肺纤维化中的关系尚不清楚。我们的研究旨在确定在PQ中毒诱导的肺纤维化中，HIF‐1α在EMT中的调节是否通过Snail和β‐catenin途径发生。66只Sprague-Dawley大鼠随机均匀分为对照组和PQ组。PQ组分别灌胃20% PQ溶液（50 mg/kg） 2、6、12、24、48和72小时。A549和RLE‐6TN细胞系在暴露于PQ之前用HIF‐1α siRNA转染48小时。我们的研究采用了Western blotting、实时定量PCR、免疫荧光、免疫组织化学等方法。在体内，HIF‐1α和α‐SMA的蛋白水平在2小时时升高，而ZO‐1（闭塞带）的水平在12小时时降低。在体外，瞬时转染HIF‐1α siRNA可导致EMT程度降低。当HIF‐α被沉默时，Snail和β‐catenin的表达水平显著降低。这些数据表明，EMT可能参与PQ中毒诱导的肺纤维化，并由HIF‐1α通过Snail和β‐catenin途径调节。缺氧诱导因子- 1α可能是治疗PQ中毒引起的肺纤维化的治疗靶点。
Paraquat (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.
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DOI：
10.1016/j.bbamcr.2013.02.029
发表时间：
2013-06
影响因子：
5.1
作者：
Han, Wei-Qing;Zhu, Qing;Hu, Junping;Li, Pin-Lan;Zhang, Fan;Li, Ningjun
通讯作者：
Li, Ningjun
影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
4.3
作者：
Higgins, Debra F.;Kimura, Kuniko;Haase, Volker H.
通讯作者：
Haase, Volker H.
影响因子：
11.2
作者：
Krishnamachary, B;Zagzag, D;Semenza, GL
通讯作者：
Semenza, GL
缺氧诱导的 Bmi1 通过 PI3K/Akt 信号促进肾小管上皮细胞间质转化和肾纤维化。
影响因子：
3.3
作者：
Du R;Xia L;Ning X;Liu L;Sun W;Huang C;Wang H;Sun S
通讯作者：
Sun S