title: Potential candidate genes for alveolar hypoxia identified by transcriptome network analysis.
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.
authors: Department of Cardiovascular Diseases, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors: Bi-li
authors: BL
authors: Zhang
authors: Rong-liang
authors: RL
authors: Xu
authors: Yong-wen
authors: YW
authors: Qin
authors: Xing
authors: X
authors: Zheng
authors: Hong
authors: H
authors: Wu
authors: Xiao-hua
authors: XH
authors: You
authors: Jiang
authors: J
authors: Cao
authors: Jian-qiang
authors: JQ
authors: Hu
authors: Xian-xian
authors: XX
authors: Zhao
mesh_terms: D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D020672:I-kappa B Proteins / Q000235:genetics; D011650:Pulmonary Alveoli; D059467:Transcriptome
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C083487:I kappa B beta protein; D020672:I-kappa B Proteins