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Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model

ABSTRACT: The structure of alveoli is critical for proper lung function, the extracellular matrix (ECM) that forms these delicate structures need to be maintained throughout life, when this fails, patients suffer from conditions such as emphysema or lung fibrosis. The alveolar walls are lined by alveolar epithelial cells (AEC), and we herein set out to examine their potential to contribute to ECM remodeling in a human three-dimensional in vitro model based on human lung ECM. Cryopreserved type 2 AEC (AEC2) isolated from healthy lungs and lungs of patients with chronic obstructive pulmonary disease (COPD) were cultured in decellularized human lung slices over a period of 13 days. AEC2 from healthy lungs were treated with transforming growth factor ß1 (TGF-ß1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were performed by RNA-sequencing, mass spectrometry and immunohistochemistry. AEC2 in our model displayed an AEC marker profile similar to freshly isolated AEC2. COPD-derived AEC2 retained expression of known disease markers such as HLA-A throughout the culture period. AEC2 matrisome expression was found not to be limited to basement membrane components but included a complex set of structural proteins found in interstitial ECM. With TGF-ß1 stimuli, AEC2 showed a change in ECM production resembling what have previously been documented in mesenchymal cells, without loss of AEC marker expression. A previously unexplored potential of AEC to directly contribute to ECM turnover is revealed, motivating a re-evaluation of the role of AEC2 in pathological lung remodeling.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Type Ii Pneumocyte

DISEASE(S): Chronic Obstructive Pulmonary Disease

SUBMITTER: Oskar Rosmark

LAB HEAD: Gunilla Westergren-Thorsson

PROVIDER: PXD034531 | Pride | 2023-06-29

REPOSITORIES: Pride

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Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model.

Rosmark Oskar O Kadefors Måns M Dellgren Göran G Karlsson Christofer C Ericsson Anders A Lindstedt Sandra S Malmström Johan J Hallgren Oskar O Larsson-Callerfelt Anna-Karin AK Westergren-Thorsson Gunilla G

Scientific reports 20230531 1

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 ev ...[more]

PMID: 37258541

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