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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 |
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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0220795</identifier><identifier>PMID: 31437169</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2019-08, Vol.14 (8), p.e0220795-e0220795</ispartof><rights>2019 Seki et al. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31437169</pmid><doi>10.1371/journal.pone.0220795</doi><orcidid>https://orcid.org/0000-0002-2113-3422</orcidid><oa>free_for_read</oa></addata></record> |
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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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