Seki, MitsuruFurukawa, NozomiKoitabashi, NorimichiObokata, MasaruConway, Simon J.Arakawa, HirokazuKurabayashi, Masahiko2019-12-312019-12-312019-08-22Seki, M., Furukawa, N., Koitabashi, N., Obokata, M., Conway, S. J., Arakawa, H., & Kurabayashi, M. (2019). Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension. PloS one, 14(8), e0220795. doi:10.1371/journal.pone.0220795https://hdl.handle.net/1805/21656Transforming 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.en-USTransforming growth factor beta (TGF-β)Pulmonary arterial hypertension (PAH)Periostin (Pn)Upregulated proteinsType I TGF-β receptor knockout miceSmall pulmonary arteries (PAs)Pulmonary artery resistanceArticle