In Su/Hx-PAH mice, upregulated Legumain activates extracellular MMP-2, leading to upregulation of TGF-β1 and increased Smad2/3 phosphorylation in PASMCs, which results in deposition of ECM proteins (COL1, FN1, and tenascin C) in pulmonary arteries.82 Here, TGFB1 is linked to pulmonary arterial hypertension.