Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model

Asthma is associated with increased deposition and altered phenotype of airway smooth muscle (ASM) cells. However, little is known about the processes responsible for these changes. It has been suggested that alterations of the extracellular matrix (ECM) contribute to the remodeling of ASM cells in...

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Autores principales:	Selma Ben Hamouda, Maria Angélica Miglino, Gustavo de Sá Schiavo Matias, Guy Beauchamp, Jean-Pierre Lavoie
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	asthma 3D culture extracellular matrix airway smooth muscle recellularization phenotype Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/978c812e678b42bf818388a881e57b68
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spelling	oai:doaj.org-article:978c812e678b42bf818388a881e57b682021-12-01T08:11:57ZAsthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model2673-610110.3389/falgy.2021.762026https://doaj.org/article/978c812e678b42bf818388a881e57b682021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/falgy.2021.762026/fullhttps://doaj.org/toc/2673-6101Asthma is associated with increased deposition and altered phenotype of airway smooth muscle (ASM) cells. However, little is known about the processes responsible for these changes. It has been suggested that alterations of the extracellular matrix (ECM) contribute to the remodeling of ASM cells in asthma. Three-dimensional matrices allow the in vitro study of complex cellular responses to different stimuli in a close-to-natural environment. Thus, we investigated the ultrastructural and genic variations of ASM cells cultured on acellular asthmatic and control bronchial matrices. We studied horses, as they spontaneously develop a human asthma-like condition (heaves) with similarities to chronic pulmonary changes observed in human asthma. Primary bronchial ASM cells from asthmatic (n = 3) and control (n = 3) horses were cultured on decellularized bronchi from control (n = 3) and asthmatic (n = 3) horses. Each cell lineage was used to recellularize six different bronchi for 41 days. Histomorphometry on HEPS-stained-recellularized matrices revealed an increased ASM cell number in the control cell/control matrix (p = 0.02) and asthmatic cell/control matrix group (p = 0.04) compared with the asthmatic cell/asthmatic matrix group. Scan electron microscopy revealed a cell invasion of the ECM. While ASM cells showed high adhesion and proliferation processes on the control ECM, the presence of senescent cells and cellular debris in the asthmatic ECM with control or asthmatic ASM cells suggested cell death. When comparing asthmatic with control cell/matrix combinations by targeted next generation sequencing, only AGC1 (p = 0.04), MYO10 (p = 0.009), JAM3 (p = 0.02), and TAGLN (p = 0.001) were differentially expressed out of a 70-gene pool previously associated with smooth muscle remodeling. To our knowledge, this is the first attempt to evaluate the effects of asthmatic ECM on an ASM cell phenotype using a biological bronchial matrix. Our results indicate that bronchial ECM health status contributes to ASM cell gene expression and, possibly, its survival.Selma Ben HamoudaMaria Angélica MiglinoGustavo de Sá Schiavo MatiasGuy BeauchampJean-Pierre LavoieFrontiers Media S.A.articleasthma3D cultureextracellular matrixairway smooth musclerecellularizationphenotypeImmunologic diseases. AllergyRC581-607ENFrontiers in Allergy, Vol 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	asthma 3D culture extracellular matrix airway smooth muscle recellularization phenotype Immunologic diseases. Allergy RC581-607
spellingShingle	asthma 3D culture extracellular matrix airway smooth muscle recellularization phenotype Immunologic diseases. Allergy RC581-607 Selma Ben Hamouda Maria Angélica Miglino Gustavo de Sá Schiavo Matias Guy Beauchamp Jean-Pierre Lavoie Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model
description	Asthma is associated with increased deposition and altered phenotype of airway smooth muscle (ASM) cells. However, little is known about the processes responsible for these changes. It has been suggested that alterations of the extracellular matrix (ECM) contribute to the remodeling of ASM cells in asthma. Three-dimensional matrices allow the in vitro study of complex cellular responses to different stimuli in a close-to-natural environment. Thus, we investigated the ultrastructural and genic variations of ASM cells cultured on acellular asthmatic and control bronchial matrices. We studied horses, as they spontaneously develop a human asthma-like condition (heaves) with similarities to chronic pulmonary changes observed in human asthma. Primary bronchial ASM cells from asthmatic (n = 3) and control (n = 3) horses were cultured on decellularized bronchi from control (n = 3) and asthmatic (n = 3) horses. Each cell lineage was used to recellularize six different bronchi for 41 days. Histomorphometry on HEPS-stained-recellularized matrices revealed an increased ASM cell number in the control cell/control matrix (p = 0.02) and asthmatic cell/control matrix group (p = 0.04) compared with the asthmatic cell/asthmatic matrix group. Scan electron microscopy revealed a cell invasion of the ECM. While ASM cells showed high adhesion and proliferation processes on the control ECM, the presence of senescent cells and cellular debris in the asthmatic ECM with control or asthmatic ASM cells suggested cell death. When comparing asthmatic with control cell/matrix combinations by targeted next generation sequencing, only AGC1 (p = 0.04), MYO10 (p = 0.009), JAM3 (p = 0.02), and TAGLN (p = 0.001) were differentially expressed out of a 70-gene pool previously associated with smooth muscle remodeling. To our knowledge, this is the first attempt to evaluate the effects of asthmatic ECM on an ASM cell phenotype using a biological bronchial matrix. Our results indicate that bronchial ECM health status contributes to ASM cell gene expression and, possibly, its survival.
format	article
author	Selma Ben Hamouda Maria Angélica Miglino Gustavo de Sá Schiavo Matias Guy Beauchamp Jean-Pierre Lavoie
author_facet	Selma Ben Hamouda Maria Angélica Miglino Gustavo de Sá Schiavo Matias Guy Beauchamp Jean-Pierre Lavoie
author_sort	Selma Ben Hamouda
title	Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model
title_short	Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model
title_full	Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model
title_fullStr	Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model
title_full_unstemmed	Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model
title_sort	asthmatic bronchial matrices determine the gene expression and behavior of smooth muscle cells in a 3d culture model
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/978c812e678b42bf818388a881e57b68
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Asthmatic Bronchial Matrices Determine the Gene Expression and Behavior of Smooth Muscle Cells in a 3D Culture Model

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