GLI1 Promotes Hypoxia Induced Pyroptosis of PASMCs and Aggravates Pulmonary Arterial Hypertension in Rats by Upregulating HDAC1 Expression.

Existing research data show that pulmonary artery smooth muscle cells (PASMCs) can play a very important role in the occurrence and development of pulmonary hypertension (PAH). Through in-depth study and analysis, we found that glioma-associated oncogene family zinc finger 1 (GLI1) has a significantly higher expression level in the nucleus and cytoplasm of hypoxic PASMCs. Next, GLI1 overexpression plasmid or small interfering RNA were transfected into hypoxic PASMCs respectively, and GLI1 promoted the migration and pyroptosis of hypoxic PASMCs, while GLI1 silencing had the opposite effect. Next, histone deacetylase 1 (HDAC1) was verified to be a binding protein of GLI1, and GLI1 promotes HDAC1 protein expression. Then, HDAC1 promoted abnormal of hypoxic PASMCs, while HDAC1 knockdown inhibited cell migration and pyroptosis. Then, the hypoxic PASMCs were transfected si-GLI1 alone or together with HDAC1-OE, and further confirm that GLI1 promotes hypoxia induced pyroptosis and abnormal proliferation of PASMCs by upregulating HDAC1 protein expression. In addition, we constructed a PAH rat model, and found that GLI1 silenced PAH rats had reduced expression of markers related to pyroptosis and smooth muscle cell proliferation in the lung tissue, and the lung injury of rats was reduced, and the lung function was significantly improved, suggesting that GLI1 silencing is beneficial to PAH in rats.