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Alveolar repair following LPS-induced injury requires cell-ECM interactions

During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severi...

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Autores principales: Sucre, Jennifer M.S., Bock, Fabian, Negretti, Nicholas M., Benjamin, John T., Gulleman, Peter M., Dong, Xinyu, Ferguson, Kimberly T., Jetter, Christopher S., Han, Wei, Liu, Yang, Kook, Seunghyi, Gokey, Jason J., Guttentag, Susan H., Kropski, Jonathan A., Blackwell, Timothy S., Zent, Roy, Plosa, Erin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443799/
https://www.ncbi.nlm.nih.gov/pubmed/37279065
http://dx.doi.org/10.1172/jci.insight.167211
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author Sucre, Jennifer M.S.
Bock, Fabian
Negretti, Nicholas M.
Benjamin, John T.
Gulleman, Peter M.
Dong, Xinyu
Ferguson, Kimberly T.
Jetter, Christopher S.
Han, Wei
Liu, Yang
Kook, Seunghyi
Gokey, Jason J.
Guttentag, Susan H.
Kropski, Jonathan A.
Blackwell, Timothy S.
Zent, Roy
Plosa, Erin J.
author_facet Sucre, Jennifer M.S.
Bock, Fabian
Negretti, Nicholas M.
Benjamin, John T.
Gulleman, Peter M.
Dong, Xinyu
Ferguson, Kimberly T.
Jetter, Christopher S.
Han, Wei
Liu, Yang
Kook, Seunghyi
Gokey, Jason J.
Guttentag, Susan H.
Kropski, Jonathan A.
Blackwell, Timothy S.
Zent, Roy
Plosa, Erin J.
author_sort Sucre, Jennifer M.S.
collection PubMed
description During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β(1)-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of β(1) integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β(1)-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in β(1) showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β(1)-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β(1)-containing integrins.
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spelling pubmed-104437992023-08-23 Alveolar repair following LPS-induced injury requires cell-ECM interactions Sucre, Jennifer M.S. Bock, Fabian Negretti, Nicholas M. Benjamin, John T. Gulleman, Peter M. Dong, Xinyu Ferguson, Kimberly T. Jetter, Christopher S. Han, Wei Liu, Yang Kook, Seunghyi Gokey, Jason J. Guttentag, Susan H. Kropski, Jonathan A. Blackwell, Timothy S. Zent, Roy Plosa, Erin J. JCI Insight Research Article During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if β(1)-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of β(1) integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, β(1)-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in β(1) showed persistently increased proliferation after injury, which was blocked by inhibiting NF-κB activation in these cells. Lineage tracing experiments revealed that β(1)-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires β(1)-containing integrins. American Society for Clinical Investigation 2023-07-24 /pmc/articles/PMC10443799/ /pubmed/37279065 http://dx.doi.org/10.1172/jci.insight.167211 Text en © 2023 Sucre et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Sucre, Jennifer M.S.
Bock, Fabian
Negretti, Nicholas M.
Benjamin, John T.
Gulleman, Peter M.
Dong, Xinyu
Ferguson, Kimberly T.
Jetter, Christopher S.
Han, Wei
Liu, Yang
Kook, Seunghyi
Gokey, Jason J.
Guttentag, Susan H.
Kropski, Jonathan A.
Blackwell, Timothy S.
Zent, Roy
Plosa, Erin J.
Alveolar repair following LPS-induced injury requires cell-ECM interactions
title Alveolar repair following LPS-induced injury requires cell-ECM interactions
title_full Alveolar repair following LPS-induced injury requires cell-ECM interactions
title_fullStr Alveolar repair following LPS-induced injury requires cell-ECM interactions
title_full_unstemmed Alveolar repair following LPS-induced injury requires cell-ECM interactions
title_short Alveolar repair following LPS-induced injury requires cell-ECM interactions
title_sort alveolar repair following lps-induced injury requires cell-ecm interactions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443799/
https://www.ncbi.nlm.nih.gov/pubmed/37279065
http://dx.doi.org/10.1172/jci.insight.167211
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