Abstract
Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening.
Highlights
Pulmonary arterial hypertension (PAH) is a rare disease of the small pulmonary arteries (PAs) characterized by raised pulmonary artery resistance, which results in a marked increase in pulmonary arterial pressure, remodeling and right ventricular hypertrophy[1]
These findings suggested that our hypoxia-induced PAH mice model was correctly established
Our study showed that Pn is strongly involved in the formation of remodeled PA, indicating that pulmonary artery smooth muscle cells (PASMCs), and various cells including extracellular matrix proteins (ECM) proteins such as Pn, are important for the pathogenesis of PAH
Summary
Pulmonary arterial hypertension (PAH) is a rare disease of the small pulmonary arteries (PAs) characterized by raised pulmonary artery resistance, which results in a marked increase in pulmonary arterial pressure, remodeling and right ventricular hypertrophy[1]. The increase in pulmonary vascular resistance is due to adventitial, medial, and intimal thickening of PAs that results from proliferation and migration of smooth muscle cell, proliferation or activation of fibroblasts, and proliferation of disorganized endothelial cell[2]. Periostin (Pn), termed osteoblast-specific factor 2, is a matricellular proteins that was initially suggested to function as a cell adhesion molecule for preosteoblasts[3].
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