Browsing by Author "Koitabashi, Norimichi"

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    Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension
    (PLOS, 2019-08-22) Seki, Mitsuru; Furukawa, Nozomi; Koitabashi, Norimichi; Obokata, Masaru; Conway, Simon J.; Arakawa, Hirokazu; Kurabayashi, Masahiko; Pediatrics, School of Medicine
    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.