Although this study did not specifically examine whether the activation of HIF itself through hypoxia is regulated by Otud6b, we found that activation of Otud6b expression with rOtud6b does increase HIF expression, which further regulates the transcription of cytokines and important proteins (such as VEGF, ET-1, etc.), which contribute to the development of PAH. The gene discussed is VEGFA; the disease is pulmonary arterial hypertension.