SMAD2 and idiopathic pulmonary arterial hypertension: On the other hand, TGF-β-treated PECs from patients with iPAH showed a more sensitive activation of the Smad1/5/8 and, to a lesser degree, Smad2/3 signaling pathways, suggesting a predominance of the TGF-β/ALK1/Smad1/5/8 signaling pathways in these cells.