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

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 l...

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Main Authors: Mitsuru Seki, Nozomi Furukawa, Norimichi Koitabashi, Masaru Obokata, Simon J Conway, Hirokazu Arakawa, Masahiko Kurabayashi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0220795
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author Mitsuru Seki
Nozomi Furukawa
Norimichi Koitabashi
Masaru Obokata
Simon J Conway
Hirokazu Arakawa
Masahiko Kurabayashi
author_facet Mitsuru Seki
Nozomi Furukawa
Norimichi Koitabashi
Masaru Obokata
Simon J Conway
Hirokazu Arakawa
Masahiko Kurabayashi
author_sort Mitsuru Seki
collection DOAJ
description 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.
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spelling doaj.art-ed327ba5a2ac49868e25db0b09257e192022-12-21T22:39:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01148e022079510.1371/journal.pone.0220795Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.Mitsuru SekiNozomi FurukawaNorimichi KoitabashiMasaru ObokataSimon J ConwayHirokazu ArakawaMasahiko KurabayashiTransforming 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.https://doi.org/10.1371/journal.pone.0220795
spellingShingle Mitsuru Seki
Nozomi Furukawa
Norimichi Koitabashi
Masaru Obokata
Simon J Conway
Hirokazu Arakawa
Masahiko Kurabayashi
Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
PLoS ONE
title Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
title_full Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
title_fullStr Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
title_full_unstemmed Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
title_short Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension.
title_sort periostin expressing cell specific transforming growth factor β inhibition in pulmonary artery prevents pulmonary arterial hypertension
url https://doi.org/10.1371/journal.pone.0220795
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