Periostin-expressing cell-specific transforming growth factor-? inhibition in pulmonary artery prevents pulmonary arterial hypertension.

ABSTRACT: Transforming growth factor beta (TGF-?) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-? 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-? 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-? signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening.

SUBMITTER: Seki M 

PROVIDER: S-EPMC6705784 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature