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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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Published in:PloS one 2019-08, Vol.14 (8), p.e0220795-e0220795
Main Authors: Seki, Mitsuru, Furukawa, Nozomi, Koitabashi, Norimichi, Obokata, Masaru, Conway, Simon J, Arakawa, Hirokazu, Kurabayashi, Masahiko
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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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subjects Animals
Biology and life sciences
Cell activation
Cell adhesion & migration
Cell Adhesion Molecules - metabolism
Cell Adhesion Molecules - pharmacology
Experiments
Extracellular matrix
Fibroblasts
Fluorescence
Growth factors
Heart
Hemodynamics
Hypertension
Hypertension, Pulmonary - metabolism
Hypoxia
Hypoxia - metabolism
Inhibition
Kinases
Lung - pathology
Lungs
Male
Medicine
Medicine and Health Sciences
Mice
Mice, Knockout
Muscle, Smooth, Vascular - metabolism
Oxygen
Pathogenesis
Pediatrics
Proteins
Pulmonary Arterial Hypertension - metabolism
Pulmonary Arterial Hypertension - physiopathology
Pulmonary arteries
Pulmonary artery
Pulmonary Artery - pathology
Pulmonary fibrosis
Pulmonary hypertension
Receptors, Transforming Growth Factor beta - metabolism
Research and Analysis Methods
Rodents
Signal Transduction
Signaling
Smad3 protein
Smooth muscle
Thickening
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta - physiology
Transforming growth factor-b
Transforming Growth Factors - metabolism
Transgenic animals
University graduates
Veins & arteries
Ventricle
title Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension
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