Faculty Opinions recommendation of Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1.

2009 ◽  
Author(s):  
Daniela Negrini
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Hypoxia Inducible Factor 1 ◽  
Mitochondrial Ros

scholarly journals Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1

2009 ◽  
Vol 297 (6) ◽  
pp. L1120-L1130 ◽  
Author(s):  
Guofei Zhou ◽  
Laura A. Dada ◽  
Minghua Wu ◽  
Aileen Kelly ◽  
Humberto Trejo ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Mitochondrial Ros ◽  
Lung Dysfunction ◽  
Tgf Β1

Patients with acute lung injury develop hypoxia, which may lead to lung dysfunction and aberrant tissue repair. Recent studies have suggested that epithelial-mesenchymal transition (EMT) contributes to pulmonary fibrosis. We sought to determine whether hypoxia induces EMT in alveolar epithelial cells (AEC). We found that hypoxia induced the expression of α-smooth muscle actin (α-SMA) and vimentin and decreased the expression of E-cadherin in transformed and primary human, rat, and mouse AEC, suggesting that hypoxia induces EMT in AEC. Both severe hypoxia and moderate hypoxia induced EMT. The reactive oxygen species (ROS) scavenger Euk-134 prevented hypoxia-induced EMT. Moreover, hypoxia-induced expression of α-SMA and vimentin was prevented in mitochondria-deficient ρ0 cells, which are incapable of ROS production during hypoxia. CoCl2 and dimethyloxaloylglycine, two compounds that stabilize hypoxia-inducible factor (HIF)-α under normoxia, failed to induce α-SMA expression in AEC. Furthermore, overexpression of constitutively active HIF-1α did not induce α-SMA. However, loss of HIF-1α or HIF-2α abolished induction of α-SMA mRNA during hypoxia. Hypoxia increased the levels of transforming growth factor (TGF)-β1, and preincubation of AEC with SB431542, an inhibitor of the TGF-β1 type I receptor kinase, prevented the hypoxia-induced EMT, suggesting that the process was TGF-β1 dependent. Furthermore, both ROS and HIF-α were necessary for hypoxia-induced TGF-β1 upregulation. Accordingly, we have provided evidence that hypoxia induces EMT of AEC through mitochondrial ROS, HIF, and endogenous TGF-β1 signaling.

scholarly journals HIF-1-miR-219-SMC4 Regulatory Pathway Promoting Proliferation and Migration of HCC under Hypoxic Condition

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yang Chen ◽  
Fei Huang ◽  
liang Deng ◽  
Xiaowei Yuan ◽  
Qiang Tao ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Condition ◽  
Regulatory Pathway ◽  
Mesenchymal Transition ◽  
Hypoxia Inducible Factor 1 ◽  
Structural Maintenance Of Chromosome ◽  
And Migration ◽  
Hcc Cells ◽  
Proliferation And Migration

This paper aims to investigate the function of structural maintenance of chromosome 4 (SMC4) in the progression of hepatocellular carcinoma (HCC) under hypoxic condition. In this study, we found that suppression of SMC4 could inhibit proliferation and migration of HCC cells through inducing G1 phase arrest and affecting process of epithelial-mesenchymal transition (EMT) under hypoxic condition. Moreover, we demonstrated that SMC4 was transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) under hypoxic condition. As SMC has been shown to be a target gene of miR-219, we observed that miR-219 was downregulated under hypoxic condition and suppression of HIF-1a could lead to the upregulation of miR-219. We also proved that miR-219 could affect the proliferation and migration of HCC cells under hypoxic condition. In conclusion, our study demonstrated a novel HIF-1-miR-219-SMC4 regulatory pathway under hypoxic condition in HCC cells.

MiRNA, a New Treatment Strategy for Pulmonary Fibrosis

2020 ◽  
Vol 21 ◽  
Author(s):  
Yanhong Liu ◽  
Hongguang Nie ◽  
Yan Ding ◽  
Yapeng Hou ◽  
Kejun Mao ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Epithelial Cell ◽  
The Elderly ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Delay In Diagnosis ◽  
Alveolar Epithelial ◽  
Epithelial Cell Apoptosis ◽  
New Treatment

: Pulmonary fibrosis (PF) is the most common chronic, progressive interstitial lung disease, mainly occurring in the elderly, with a median survival of 2-4 years after diagnosis. Its high mortality rate attributes to the delay in diagnosis due to its generic symptoms, and more importantly, to the lack of effective treatments. MicroRNAs (miRNAs) are a class of small non-coding RNAs that involve in many essential cellular processes, including extracellular matrix remodeling, alveolar epithelial cell apoptosis, epithelial-mesenchymal transition, etc. We summarized the dysregulated miRNAs in TGF-β signaling pathway-mediated PF in recent years with dual effects, such as anti-fibrotic let-7 family and pro-fibrotic miR-21 members. Therefore, this review will set out the latest application of miRNAs to provide a new direction for PF treatment.

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