Fig. 5
Hypoxia-associated proteins and target protein selection for Combined mechanism. a Volcano plot of hypoxia-associated proteins. Hypoxia-associated proteins refer to DEPs in Control group subjects (n = 6) between baseline and post-hypoxia. The proteins are showed according to their log2 (fold change) (X-axis) and significance (Y-axis: − log10 p value). Red dots represent proteins with a significant fold change > 2; green dots, proteins with a significant fold change < 0.5; black dots, proteins with no significant change. A total of 30 hypoxia-associated proteins were identified, among which 22 were upregulated and 8 were downregulated. b Heatmap of expression profiling of hypoxia-associated proteins. Each line represents a sample, each column is a protein, and the colors represent different expression levels. c Gene Ontology (GO) term enrichment analysis of hypoxia-associated proteins. X-axis indicates the number of proteins; Y-axis represents the different GO terms. d Protein–protein association network of hypoxia-associated proteins by STRING analysis. The network nodes are proteins, which were clustered to four clusters using kmeans clustering. The proteins in each cluster contributed to a common function: red nodes for inflammation, green for extracellular matrix restructuring, yellow for cell adhesion, and blue for immune cell function. Differently colored lines represent different types of evidence used in predicting the associations. e Venn diagrams of hypoxia-associated proteins between baseline and pre-hypoxia (DEPs group 1) and between baseline and post-hypoxia (DEPs group 2) in each of the Acetazolamide (n = 6), Rapid-Ripc (n = 6), and Combined group (n = 6). A total of fifteen proteins in the overlapping region were focused. After reviewing the literature and considering the fluorescence signal intensity, PDGF-AB was selected for further validation. f Expression of PDGF-AB. X-axis represents different groups; Y-axis represents fold change. N = 6 in each group. AZA, acetazolamide. *P < 0.05, **P < 0.01