Table 4.
Commonly activated or inhibited regulators in rat hypoxia lungs and human pulmonary arterial hypertension (67) lungs
| Upstream Regulator | Molecule Type | Rat HH/RARA Lung |
Human PAH/FD Lung |
||
|---|---|---|---|---|---|
| Adjusted P Value | Activation z-Score | Adjusted P Value | Activation z-Score | ||
| β-Estradiol | Chemical | 2.27E-26 | ↑ | 3.18E-16 | Inhibited |
| Dexamethasone | Chemical | 2.54E-17 | ↑ | 1.58E-14 | Inhibited |
| Lipopolysaccharide | Chemical | 1.72E-23 | Inhibited | 5.64E-09 | ↓ |
| IFNG | Cytokine | 2.99E-12 | Inhibited | 4.09E-05 | ↓ |
| IL10 | Cytokine | 2.17E-09 | ↓ | 7.91E-06 | Inhibited |
| IL1B | Cytokine | 1.02E-14 | Inhibited | 1.13E-03 | ↓ |
| IL6 | Cytokine | 1.91E-16 | ↓ | 6.59E-03 | ↓ |
| TNF | Cytokine | 7.82E-19 | Inhibited | 6.00E-11 | ↓ |
| TGFB1 | Growth factor | 5.11E-14 | Inhibited | 1.02E-08 | ↑ |
| ESR1 | Receptor | 2.24E-08 | ↑ | 2.65E-06 | ↑ |
| ERBB2 | Kinase | 4.57E-09 | Activated | 2.08E-03 | ↑ |
| KLF2 | Transcription regulator | 5.23E-10 | ↑ | 1.24E-02 | Inhibited |
| NFKBIA | Transcription regulator | 2.99E-12 | ↑ | 5.76E-03 | ↑ |
Rat lung upstream regulators were compared with predictions from our recently published human PAH transcriptome data set (29). Expression of regulators in hypoxic rat lungs is compared with lungs from rats exposed to in utero and postnatal room air (HH/RARA). Expression of regulators from PAH lungs is compared with expression in failed lung transplant donor (FD) lungs. Adjusted P values indicate degree of pathway enrichment from the differentially expressed gene lists. Z-scores indicate predicted pathway direction with “Inhibited”/”Activated” indicating z-scores > |2.0|, and up or down arrows indicating z-scores < |2.0|. Note a global pattern of immune downregulation that is shared between rat and human, as well as common LPS, ESR1, ERBB2, and NFKBIA regulation patterns. HH, in utero and postnatal hypoxia; RARA, in utero and postnatal room air. See Table 2 for full names of regulators.