SMAD2 and pulmonary arterial hypertension: In lung tissues of MCT-PAH rats, EGF levels were elevated, and Calpain-1 and Calpain-2 were upregulated.80 Additionally, Calpain-4 was upregulated in the lungs of mice with hypoxia-PH.80 These changes resulted in increased levels of PDGF, activation of the TGF-β1/Smad2/3 pathway, excessive deposition of COL1, and thickening of the smooth muscle layer of pulmonary arterioles, contributing to pulmonary vascular remodeling and the development of PH.80