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CFTR dysfunction increases endoglin and TGF-ß signaling in airway epithelia.
Nicola, Teodora; Kabir, Farruk L; Coric, Tatjana; Wall, Stephanie B; Zhang, Weifeng; James, Masheika; MacEwen, Mark; Ren, Changchun; Halloran, Brian; Ambalavanan, Namasivayam; Harris, William T.
Afiliación
  • Nicola T; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Kabir FL; Division of Pediatric Pulmonology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Coric T; Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama.
  • Wall SB; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Zhang W; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • James M; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • MacEwen M; Division of Pediatric Pulmonology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Ren C; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Halloran B; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Ambalavanan N; Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
  • Harris WT; Division of Pediatric Pulmonology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Physiol Rep ; 7(4): e13977, 2019 02.
Article en En | MEDLINE | ID: mdl-30806029
Endoglin (ENG) regulates signaling by transforming growth factor-ß (TGF-ß), a genetic modifier of cystic fibrosis (CF) lung disease severity. We hypothesized that ENG mediates TGF-ß pathobiology in CF airway epithelia. Comparing CF and non-CF human lungs, we measured ENG by qPCR, immunoblotting and ELISA. In human bronchial epithelial cell lines (16HBE), we used CFTR siRNA knockdown and functional inhibition (CFTRINH -172) to connect loss of CFTR to ENG synthesis. Plasmid overexpression of ENG assessed the direct effect of ENG on TGF-ß transcription and signal amplification in 16HBE cells. We found ENG protein to be increased more than fivefold both in human CF bronchoalveolar fluid (BALF) and human CF lung homogenates. ENG transcripts were increased threefold in CF, with a twofold increase in TGF-ß signaling. CFTR knockdown in 16HBE cells tripled ENG transcription and doubled protein levels with corresponding increases in TGF-ß signaling. Plasmid overexpression of ENG alone nearly doubled TGF-ß1 mRNA and increased TGF-ß signaling in 16HBE cells. These experiments identify that loss of CFTR function increases ENG expression in CF epithelia and amplifies TGF-ß signaling. Targeting ENG may offer a novel therapeutic opportunity to address TGF-ß associated pathobiology in CF.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Fibrosis Quística / Células Epiteliales Alveolares / Endoglina Tipo de estudio: Prognostic_studies Límite: Child / Humans Idioma: En Revista: Physiol Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Fibrosis Quística / Células Epiteliales Alveolares / Endoglina Tipo de estudio: Prognostic_studies Límite: Child / Humans Idioma: En Revista: Physiol Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos