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Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity
The interaction between extracellular matrix (ECM) and epithelial cells plays a key role in lung development. Our studies found that mice with conditional integrin β4 (ITGB4) knockout presented lung dysplasia and increased stiffness of lung tissues. In accordance with our previous studies regarding...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926985/ https://www.ncbi.nlm.nih.gov/pubmed/35309934 http://dx.doi.org/10.3389/fcell.2022.845440 |
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author | Chi, Yinxiu Chen, Yu Jiang, Wang Huang, Wenjie Ouyang, Mingxing Liu, Lei Pan, Yan Li, Jingjing Qu, Xiangping Liu, Huijun Liu, Chi Deng, Linhong Qin, Xiaoqun Xiang, Yang |
author_facet | Chi, Yinxiu Chen, Yu Jiang, Wang Huang, Wenjie Ouyang, Mingxing Liu, Lei Pan, Yan Li, Jingjing Qu, Xiangping Liu, Huijun Liu, Chi Deng, Linhong Qin, Xiaoqun Xiang, Yang |
author_sort | Chi, Yinxiu |
collection | PubMed |
description | The interaction between extracellular matrix (ECM) and epithelial cells plays a key role in lung development. Our studies found that mice with conditional integrin β4 (ITGB4) knockout presented lung dysplasia and increased stiffness of lung tissues. In accordance with our previous studies regarding the functions of ITGB4 in bronchial epithelial cells (BECs), we hypothesize that the decreased ITGB4 expression during embryonic stage leads to abnormal ECM remodeling and increased tissue stiffness, thus impairing BECs motility and compromising lung development. In this study, we examined lung tissue stiffness in normal and ITGB4 deficiency mice using Atomic Force Microscopy (AFM), and demonstrated that ITGB4 deficiency resulted in increased lung tissue stiffness. The examination of ECM components collagen, elastin, and lysyl oxidase (LOX) family showed that the expression of type VI collagen, elastin and LOXL4 were significantly elevated in the ITGB4-deficiency mice, compared with those in normal groups. Airway epithelial cell migration and proliferation capacities on normal and stiff substrates were evaluated through video-microscopy and flow cytometry. The morphology of the cytoskeleton was detected by laser confocal microscopy, and RhoA activities were determined by fluorescence resonance energy transfer (FRET) microscopy. The results showed that migration and proliferation of ITGB4 deficiency cells were noticeably inhibited, along decreased cytoskeleton stabilization, and hampered RhoA activity, especially for cells cultured on the stiff substrate. These results suggest that decreased ITGB4 expression results in increased lung tissue stiffness and impairs the adaptation of bronchial epithelial cells to substrate stiffness, which may be related to the occurrence of broncho pulmonary dysplasia. |
format | Online Article Text |
id | pubmed-8926985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89269852022-03-18 Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity Chi, Yinxiu Chen, Yu Jiang, Wang Huang, Wenjie Ouyang, Mingxing Liu, Lei Pan, Yan Li, Jingjing Qu, Xiangping Liu, Huijun Liu, Chi Deng, Linhong Qin, Xiaoqun Xiang, Yang Front Cell Dev Biol Cell and Developmental Biology The interaction between extracellular matrix (ECM) and epithelial cells plays a key role in lung development. Our studies found that mice with conditional integrin β4 (ITGB4) knockout presented lung dysplasia and increased stiffness of lung tissues. In accordance with our previous studies regarding the functions of ITGB4 in bronchial epithelial cells (BECs), we hypothesize that the decreased ITGB4 expression during embryonic stage leads to abnormal ECM remodeling and increased tissue stiffness, thus impairing BECs motility and compromising lung development. In this study, we examined lung tissue stiffness in normal and ITGB4 deficiency mice using Atomic Force Microscopy (AFM), and demonstrated that ITGB4 deficiency resulted in increased lung tissue stiffness. The examination of ECM components collagen, elastin, and lysyl oxidase (LOX) family showed that the expression of type VI collagen, elastin and LOXL4 were significantly elevated in the ITGB4-deficiency mice, compared with those in normal groups. Airway epithelial cell migration and proliferation capacities on normal and stiff substrates were evaluated through video-microscopy and flow cytometry. The morphology of the cytoskeleton was detected by laser confocal microscopy, and RhoA activities were determined by fluorescence resonance energy transfer (FRET) microscopy. The results showed that migration and proliferation of ITGB4 deficiency cells were noticeably inhibited, along decreased cytoskeleton stabilization, and hampered RhoA activity, especially for cells cultured on the stiff substrate. These results suggest that decreased ITGB4 expression results in increased lung tissue stiffness and impairs the adaptation of bronchial epithelial cells to substrate stiffness, which may be related to the occurrence of broncho pulmonary dysplasia. Frontiers Media S.A. 2022-03-03 /pmc/articles/PMC8926985/ /pubmed/35309934 http://dx.doi.org/10.3389/fcell.2022.845440 Text en Copyright © 2022 Chi, Chen, Jiang, Huang, Ouyang, Liu, Pan, Li, Qu, Liu, Liu, Deng, Qin and Xiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Chi, Yinxiu Chen, Yu Jiang, Wang Huang, Wenjie Ouyang, Mingxing Liu, Lei Pan, Yan Li, Jingjing Qu, Xiangping Liu, Huijun Liu, Chi Deng, Linhong Qin, Xiaoqun Xiang, Yang Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity |
title | Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity |
title_full | Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity |
title_fullStr | Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity |
title_full_unstemmed | Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity |
title_short | Deficiency of Integrin β4 Results in Increased Lung Tissue Stiffness and Responds to Substrate Stiffness via Modulating RhoA Activity |
title_sort | deficiency of integrin β4 results in increased lung tissue stiffness and responds to substrate stiffness via modulating rhoa activity |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926985/ https://www.ncbi.nlm.nih.gov/pubmed/35309934 http://dx.doi.org/10.3389/fcell.2022.845440 |
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