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Dichotomous role of integrin-ß5 in lung endothelial cells.
Blanchard, Neil; Link, Patrick A; Farkas, Daniela; Harmon, Brennan; Hudson, Jaylen; Bogamuwa, Srimathi; Piper, Bryce; Authelet, Kayla; Cool, Carlyne D; Heise, Rebecca L; Freishtat, Robert; Farkas, Laszlo.
Afiliación
  • Blanchard N; Department of Orthopedic Surgery University of Virginia Charlottesville Virginia USA.
  • Link PA; Departments of Physiology and Biomedical Engineering Mayo Clinic Rochester Michigan USA.
  • Farkas D; Department of Biomedical Engineering, School of Engineering Virginia Commonwealth University Charlottesville Virginia USA.
  • Harmon B; Division of Pulmonary Disease, College of Medicine, Department of Internal Medicine, Critical Care & Sleep Medicine, Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA.
  • Hudson J; Department of Pediatrics, Division of Emergency Medicine Children's National Health System Washington District of Columbia USA.
  • Bogamuwa S; Division of Pulmonary Disease, College of Medicine, Department of Internal Medicine, Critical Care & Sleep Medicine, Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA.
  • Piper B; Division of Pulmonary Disease, College of Medicine, Department of Internal Medicine, Critical Care & Sleep Medicine, Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA.
  • Authelet K; Division of Pulmonary Disease, College of Medicine, Department of Internal Medicine, Critical Care & Sleep Medicine, Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Columbus Ohio USA.
  • Cool CD; Department of Pediatrics, Division of Emergency Medicine Children's National Health System Washington District of Columbia USA.
  • Heise RL; Department of Pathology University of Colorado at Denver Denver Colorado USA.
  • Freishtat R; Department of Biomedical Engineering, School of Engineering Virginia Commonwealth University Charlottesville Virginia USA.
  • Farkas L; Department of Pediatrics, Division of Emergency Medicine Children's National Health System Washington District of Columbia USA.
Pulm Circ ; 12(4): e12156, 2022 Oct.
Article en En | MEDLINE | ID: mdl-36438452
Pulmonary arterial hypertension (PAH) is a progressive, devastating disease, and its main histological manifestation is an occlusive pulmonary arteriopathy. One important functional component of PAH is aberrant endothelial cell (EC) function including apoptosis-resistance, unchecked proliferation, and impaired migration. The mechanisms leading to and maintaining physiologic and aberrant EC function are not fully understood. Here, we tested the hypothesis that in PAH, ECs have increased expression of the transmembrane protein integrin-ß5, which contributes to migration and survival under physiologic and pathological conditions, but also to endothelial-to-mesenchymal transition (EnMT). We found that elevated integrin-ß5 expression in pulmonary artery lesions and lung tissue from PAH patients and rats with PH induced by chronic hypoxia and injection of CD117+ rat lung EC clones. These EC clones exhibited elevated expression of integrin-ß5 and its heterodimerization partner integrin-αν and showed accelerated barrier formation. Inhibition of integrin-ανß5 in vitro partially blocked transforming growth factor (TGF)-ß1-induced EnMT gene expression in rat lung control ECs and less in rat lung EC clones and human lung microvascular ECs. Inhibition of integrin-ανß5 promoted endothelial dysfunction as shown by reduced migration in a scratch assay and increased apoptosis in synergism with TGF-ß1. In vivo, blocking of integrin-ανß5 exaggerated PH induced by chronic hypoxia and CD117+ EC clones in rats. In summary, we found a role for integrin-ανß5 in lung endothelial survival and migration, but also a partial contribution to TGF-ß1-induced EnMT gene expression. Our results suggest that integrin-ανß5 is required for physiologic function of ECs and lung vascular homeostasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pulm Circ Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pulm Circ Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos