Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model
Abstract Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chroni...
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Nature Portfolio
2023-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35011-z |
| _version_ | 1797811564733005824 |
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| author | Oskar Rosmark Måns Kadefors Göran Dellgren Christofer Karlsson Anders Ericsson Sandra Lindstedt Johan Malmström Oskar Hallgren Anna-Karin Larsson-Callerfelt Gunilla Westergren-Thorsson |
| author_facet | Oskar Rosmark Måns Kadefors Göran Dellgren Christofer Karlsson Anders Ericsson Sandra Lindstedt Johan Malmström Oskar Hallgren Anna-Karin Larsson-Callerfelt Gunilla Westergren-Thorsson |
| author_sort | Oskar Rosmark |
| collection | DOAJ |
| description | Abstract Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chronic obstructive pulmonary disease (COPD) afflicted lungs were cultured in decellularized healthy human lung slices for 13 days. Healthy-derived AEC2 were treated with transforming growth factor ß1 (TGF-β1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were evaluated by RNA-sequencing, mass spectrometry and immunohistochemistry. The AEC2 displayed an AEC marker profile similar to freshly isolated AEC2 throughout the 13-day culture period. COPD-derived AECs proliferated as healthy AECs with few differences in gene and protein expression while retaining increased expression of disease marker HLA-A. The AEC2 expressed basement membrane components and a complex set of interstitial ECM proteins. TGF-β1 stimuli induced a significant change in interstitial ECM production from AEC2 without loss of specific AEC marker expression. This study reveals a previously unexplored potential of AEC to directly contribute to ECM turnover by producing interstitial ECM proteins, motivating a re-evaluation of the role of AEC2 in pathological lung remodelling. |
| first_indexed | 2024-03-13T07:25:38Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:25:38Z |
| publishDate | 2023-05-01 |
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| series | Scientific Reports |
| spelling | doaj.art-b001df24185b40ff860f70d73b56da862023-06-04T11:25:54ZengNature PortfolioScientific Reports2045-23222023-05-0113111710.1038/s41598-023-35011-zAlveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D modelOskar Rosmark0Måns Kadefors1Göran Dellgren2Christofer Karlsson3Anders Ericsson4Sandra Lindstedt5Johan Malmström6Oskar Hallgren7Anna-Karin Larsson-Callerfelt8Gunilla Westergren-Thorsson9Lung Biology, Department of Experimental Medical Science, Lund UniversityLung Biology, Department of Experimental Medical Science, Lund UniversityTransplant Institute and Department of Cardiothoracic Surgery, Sahlgrenska University HospitalDivision of Infection Medicine, Department of Clinical Sciences, Lund UniversityBlekinge HospitalDepartment of Thoracic Surgery, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences, Lund UniversityDivision of Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund UniversityLung Biology, Department of Experimental Medical Science, Lund UniversityLung Biology, Department of Experimental Medical Science, Lund UniversityAbstract Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chronic obstructive pulmonary disease (COPD) afflicted lungs were cultured in decellularized healthy human lung slices for 13 days. Healthy-derived AEC2 were treated with transforming growth factor ß1 (TGF-β1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were evaluated by RNA-sequencing, mass spectrometry and immunohistochemistry. The AEC2 displayed an AEC marker profile similar to freshly isolated AEC2 throughout the 13-day culture period. COPD-derived AECs proliferated as healthy AECs with few differences in gene and protein expression while retaining increased expression of disease marker HLA-A. The AEC2 expressed basement membrane components and a complex set of interstitial ECM proteins. TGF-β1 stimuli induced a significant change in interstitial ECM production from AEC2 without loss of specific AEC marker expression. This study reveals a previously unexplored potential of AEC to directly contribute to ECM turnover by producing interstitial ECM proteins, motivating a re-evaluation of the role of AEC2 in pathological lung remodelling.https://doi.org/10.1038/s41598-023-35011-z |
| spellingShingle | Oskar Rosmark Måns Kadefors Göran Dellgren Christofer Karlsson Anders Ericsson Sandra Lindstedt Johan Malmström Oskar Hallgren Anna-Karin Larsson-Callerfelt Gunilla Westergren-Thorsson Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model Scientific Reports |
| title | Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model |
| title_full | Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model |
| title_fullStr | Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model |
| title_full_unstemmed | Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model |
| title_short | Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model |
| title_sort | alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3d model |
| url | https://doi.org/10.1038/s41598-023-35011-z |
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