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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; Kadefors, Måns; Dellgren, Göran; Karlsson, Christofer; Ericsson, Anders; Lindstedt, Sandra; Malmström, Johan; Hallgren, Oskar; Larsson-Callerfelt, Anna-Karin; Westergren-Thorsson, Gunilla.
Afiliación
  • Rosmark O; Lung Biology, Department of Experimental Medical Science, Lund University, BMC C12, 22184, Lund, Sweden. Oskar.Rosmark@med.lu.se.
  • Kadefors M; Lung Biology, Department of Experimental Medical Science, Lund University, BMC C12, 22184, Lund, Sweden.
  • Dellgren G; Transplant Institute and Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Karlsson C; Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Ericsson A; Blekinge Hospital, Karlskrona, Sweden.
  • Lindstedt S; Department of Thoracic Surgery, Lund University, Lund, Sweden.
  • Malmström J; Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Hallgren O; Division of Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Larsson-Callerfelt AK; Lung Biology, Department of Experimental Medical Science, Lund University, BMC C12, 22184, Lund, Sweden. Anna-Karin.Larsson_Callerfelt@med.lu.se.
  • Westergren-Thorsson G; Lung Biology, Department of Experimental Medical Science, Lund University, BMC C12, 22184, Lund, Sweden.
Sci Rep ; 13(1): 8801, 2023 05 31.
Article en En | MEDLINE | ID: mdl-37258541
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-ß1) 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-ß1 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / Células Epiteliales Alveolares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / Células Epiteliales Alveolares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido