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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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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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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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-16T07:28:28Z |
publishDate | 2019-01-01 |
publisher | Public Library of Science (PLoS) |
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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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