Potential Candidate Genes for Alveolar Hypoxia Identified by Transcriptome Network Analysis

Bi-Li Zhang,Jian-Qiang Hu,Rong-Liang Xu,Xiao-Hua You,Hong Wu,Jiang Cao,Xing Zheng,Yong-Wen Qin,Xian-Xian Zhao

doi:10.3390/medicina48110084

Bi-Li Zhang, Jian-Qiang Hu + Show 7 more

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https://doi.org/10.3390/medicina48110084

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Abstract

BACKGROUND. Alveolar hypoxia is an important condition related to many disorders such as chronic pulmonary hypertension, pulmonary vasoconstriction, and pulmonary vascular remodeling. The aim of present study was to disclose the biological response and the potential transcriptome networks regulating the hypoxia response in the lungs. MATERIALS AND METHODS. In this study, the microarray dataset GSE11341 was used to construct a regulatory network and identify the potential genes related to alveolar hypoxia. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were also performed. RESULTS. Hypoxia inducible factor 1 alpha (HIF-1α), peroxisome proliferator-activated receptor gamma (PPARγ), and nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB) were to be the hub nodes in the transcriptome network. HIF-1α may regulate potassium voltage-gated channel, shaker-related subfamily, member (5KCNA5), solute carrier family 2 (facilitated glucose transporter), member (1SLC2A1), and heme oxygenase (decycling) 1 (HMOX1) expression through the regulation of membrane potential, glucose metabolism, and anti-inflammation pathways. HMOX-1 mediates signaling pathways that relate to NF-кB. CCND1 (cyclin D1) expression could be regulated by PPARγ and HIF-1α via the cell cycle pathway. In addition, new transcriptional factors and target genes, such as phosphofructokinase (PFKL, liver), aldolase A (ALDOA, fructose-bisphosphate), and trefoil factor 3 (intestinal) (TFF3), were also identified. CONCLUSIONS. Transcriptome network analysis is a helpful method for the identification of the candidate genes in alveolar hypoxia. The KEGG pathway and GO term analysis are beneficial in the prediction of the underlying molecular mechanism of these identified genes in alveolar hypoxia.

Highlights

Alveolar hypoxia is a pathological condition when alveolar epithelial cells are exposed to much lower oxygen tensions due to high altitude or the consequence of hypoventilation related to a central nervous disorder, obstructive airway diseases, or pulmonary edema from heart failure or acute lung injury [1]
Transcriptome network analysis is a helpful method for the identification of the candidate genes in alveolar hypoxia
The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analysis are beneficial in the prediction of the underlying molecular mechanism of these identified genes in alveolar hypoxia

Summary

Introduction

Alveolar hypoxia is a pathological condition when alveolar epithelial cells are exposed to much lower oxygen tensions due to high altitude or the consequence of hypoventilation related to a central nervous disorder, obstructive airway diseases, or pulmonary edema from heart failure or acute lung injury [1]. There are 2 general mechanisms that cells invoke during hypoxia to prevent oxygen depletion. Cells attempt to maintain ATP synthesis by increasing anaerobic glycolysis. Hypoxia has been shown to stimulate glucose transport into cells, which is in association with an increase in the glucose transporter, GLUT1 [3]. In addition to the up-regulation of glycolysis, alveolar epithelial cells induce vascular endothelial growth factor (VEGF) by HIF-1 during hypoxia [4]

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