NRF1 and chronic obstructive pulmonary disease: In addition, p65 phosphorylation and the target gene Il6 were significantly upregulated in COPD group and further upregulated in GD-COPD group, while they were downregulated in GD-T-COPD group compared to GD-COPD group (Figure 6D and G), demonstrating that testosterone affected p65 transcription through NRF1 and p65 activation.