1. Unique mechanisms of connective tissue growth factor regulation in airway smooth muscle in asthma: Relationship with airway remodelling
- Author
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Qi Ge, Joanne Van der Velden, Cornelis J. Vermeulen, Alan James, Rob van de Velde, Alen Faiz, Sonia Sawant, Junfei Wang, Brian G. Oliver, Nick H. T. ten Hacken, John G. Elliot, Kenneth J. Snibson, Liang Dong, Dikaia Xenaki, Janette K. Burgess, Anthony W. Ashton, Maarten van den Berge, Wim Timens, Groningen Research Institute for Asthma and COPD (GRIAC), Lifestyle Medicine (LM), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
- Subjects
Male ,0301 basic medicine ,RNA Stability ,medicine.medical_treatment ,PHENOTYPE ,DISEASE ,Basement Membrane ,FACTOR CTGF/CCN2 ,0302 clinical medicine ,FACTOR GENE ,Gene expression ,connective tissue growth factor ,Myocyte ,Promoter Regions, Genetic ,Base Pairing ,Lung ,Aged, 80 and over ,Regulation of gene expression ,integumentary system ,Chemistry ,Pyroglyphidae ,PROLIFERATION ,STIFFNESS ,Middle Aged ,respiratory system ,airway smooth muscle ,3. Good health ,medicine.anatomical_structure ,Airway Remodeling ,Molecular Medicine ,Female ,Original Article ,ALVEOLAR EPITHELIAL-CELLS ,Adult ,Biochemistry & Molecular Biology ,Adolescent ,Myocytes, Smooth Muscle ,Connective tissue ,airway remodelling ,FACTOR EXPRESSION ,Young Adult ,03 medical and health sciences ,EXTRACELLULAR-MATRIX ,medicine ,Animals ,Humans ,Aged ,Basement membrane ,Sheep ,Growth factor ,Connective Tissue Growth Factor ,Muscle, Smooth ,Original Articles ,Cell Biology ,asthma ,Molecular biology ,Asthma ,respiratory tract diseases ,CTGF ,030104 developmental biology ,Gene Expression Regulation ,030228 respiratory system ,CTGF EXPRESSION ,Transforming growth factor - Abstract
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues. This finding was replicated in a sheep model of allergic airways disease. In vitro, transforming growth factor (TGF)-β increased CTGF expression both in NA- and A-ASM cells but the expression was higher in A-ASM at both the mRNA and protein level as assessed by PCR and Western blot. Transfection of CTGF promoter-luciferase reporter constructs into NA- and A-ASM cells indicated that no region of the CTGF promoter (−1500 to +200 bp) displayed enhanced activity in the presence of TGF-β. However, in silico analysis of the CTGF promoter suggested that distant transcription factor binding sites may influence CTGF promoter activation by TGF-β in ASM cells. The discord between promoter activity and mRNA expression was also explained, in part, by differential post-transcriptional regulation in A-ASM cells due to enhanced mRNA stability for CTGF. In patients, higher CTGF gene expression in bronchial biopsies was correlated with increased basement membrane thickness indicating that the enhanced CTGF expression in A-ASM may contribute to airway remodelling in asthma.
- Published
- 2018