Pathologic role of peptidyl-prolyl isomerase Pin1 in pulmonary artery remodeling.

Peptidyl-prolyl isomerase Pin1 is crucial for cell proliferation, but its role in pulmonary artery remodeling (PAR) is unclear. In the present study, we aimed to evaluate the expression and contribution of Pin1 in PAR. Treatment with Pin1 inhibitor Juglone or Pin1-specific siRNAs ameliorated the expression of Pin1 and proliferating cell nuclear antigen (PCNA) in human pulmonary artery smooth muscle cells (PASMCs) in vitro, and Juglone treatment arrested the cell cycle at the G1 phase. Treatment with transforming growth factor β1 (TGF-β1) also enhanced Pin1 expression and PASMC proliferation. Immunohistochemical staining revealed that Pin1 and PCNA expression levels were increased and positively correlated with each other in PAR samples from humans and monocrotaline-treated Sprague-Dawley rats; these proteins were mainly localized in arteries undergoing remodeling, as well as inflammatory cells, and hyperplastic bronchial epithelial cells. Intraperitoneal injection of Juglone also led to morphologic and hemodynamic changes in PAR rats. Additionally, PAR rats displayed higher serum and lung TGF-β1 levels compared with controls, while administration of Juglone to PAR rats suppressed serum and lung TGF-β1 levels. The findings in this study suggest that TGF-β1 and Pin1 constitute a positive feedback loop, which plays an important role in the pathophysiology of PAR.