Upregulation of TGF-β1/3 and PAI-1 expression in lung tissues of MCT-PAH rats increases Smad2 phosphorylation, leading to increased expression of IL-6, IL-1β, and ICAM.89 Bouchet et al. found that stimulating human PASMCs with IL-1β and PAECs with H2O2 upregulates TGF-β1. This evidence concerns the gene SMAD2 and pulmonary arterial hypertension.