Inhibitor of growth 4 (ING4) inhibits hypoxia-induced EMT by decreasing HIF-1α and snail in HK2 cells

被引:16
作者
Lu, Lingling [1 ,2 ]
Li, Jing [2 ]
Le, Yuan [2 ]
Jiang, Hong [1 ]
机构
[1] China Med Univ, Dept Pediat, Affiliated Hosp 1, 155 North Nanjing St, Shenyang 110001, Liaoning, Peoples R China
[2] Jinzhou Med Univ, Dept Pediat, Affiliated Hosp 1, Jinzhou 121001, Liaoning, Peoples R China
关键词
ING4; Hypoxia; EMT; HIF-1; alpha; Snail; E-CADHERIN; TUMOR; EXPRESSION; FIBROSIS; PROGRESSION; METASTASIS; INVASION; ACTIVATION; TRANSITION; MECHANISM;
D O I
10.1016/j.acthis.2019.06.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Renal fibrosis is a common mechanism that leads to all kidney diseases and Epithelial-mesenchymal transition (EMT) is considered as one of the potential mechanisms of renal fibrosis. Inhibitor of growth 4 (ING4) was reported to involve in several diseases; especially it was negatively correlated with lung fibrogenesis parameters. However, the role of ING4 and underlying mechanisms in EMT are still unknown. In this study, we used a UUO rat model to mimic renal fibrosis, which was examined by Masson and HE staining analysis. To explore the effects of ING4 on hypoxia-induced EMT, HK2 cells were treated with hypoxia to induce EMT and ING4 was over-expressed in hypoxia-treated HK2 cells by transfection of pEGFP-N1-ING4. MTT assay was used to describe the cell viability of HK2 cells under the hypoxic condition. The expression levels of ING4, hypoxia-inducible factor-1 alpha (HIF-1 alpha), and EMT markers (E-cadherin, N-cadherin and vimentin) were examined in vivo and in vitro by western blot, qRT-PCR, immunohistochemical staining or Immunofluorescence. Our results showed that, in a UUO rat model, ING4 was decreased and EMT was developed with reduction in E-cadherin and increase in N-cadherin and vimentin, suggesting a significant association between ING4 expression and EMT. Under hypoxia, E-cadherin was down-regulated and N-cadherin and vimentin were up-regulated, indicating that hypoxia induced EMT in HK2 cells. Nonetheless, changes in the expression of EMT biomarkers were inhibited by over-expression of ING4. Moreover, over-expressing ING4 decreased the expression of HIF-1 alpha and snail in HK2 cells. These findings suggest that ING4 may inhibit hypoxia-induced EMT via decreasing HIF-1 alpha and snail in HK2 cells, indicating the potential of ING4 as a therapeutic target for renal fibrosis.
引用
收藏
页码:695 / 703
页数:9
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