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Unique mechanisms of connective tissue growth factor regulation in airway smooth muscle in asthma: Relationship with airway remodelling
- Source :
- Journal of Cellular and Molecular Medicine, Journal of cellular and molecular medicine, 22(5), 2826-2837. Wiley
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
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.
- 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
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....0d34c3ddfb128be4c2a7c0789f68a3bb