Brain-derived neurotrophic factor and airway fibrosis in asthma

American Journal of Physiology. Lung Cellular and Molecular Physiology
Michelle R FreemanY S Prakash

Abstract

Airway remodeling in asthma driven by inflammation involves proliferation of epithelial cells and airway smooth muscle (ASM), as well as enhanced extracellular matrix (ECM) generation and deposition, i.e., fibrosis. Accordingly, understanding profibrotic mechanisms is important for developing novel therapeutic strategies in asthma. Recent studies, including our own, have suggested a role for locally produced growth factors such as brain-derived neurotrophic factor (BDNF) in mediating and modulating inflammation effects. In this study, we explored the profibrotic influence of BDNF in the context of asthma by examining expression, activity, and deposition of ECM proteins in primary ASM cells isolated from asthmatic vs. nonasthmatic patients. Basal BDNF expression and secretion, and levels of the high-affinity BDNF receptor TrkB, were higher in asthmatic ASM. Exogenous BDNF significantly increased ECM production and deposition, especially of collagen-1 and collagen-3 (less so fibronectin) and the activity of matrix metalloproteinases (MMP-2, MMP-9). Exposure to the proinflammatory cytokine TNFα significantly increased BDNF secretion, particularly in asthmatic ASM, whereas no significant changes were observed with IL-13. Chelation ...Continue Reading

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Citations

Oct 24, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rodney D BrittY S Prakash
Jun 6, 2019·Physiology·L E M Kistemaker, Y S Prakash
Nov 5, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Arjun SinghSatish Rattan
Oct 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nilesh Sudhakar AmbhoreVenkatachalem Sathish
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Feb 25, 2021·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Arjun SinghSatish Rattan
Apr 2, 2021·Frontiers in Physiology·Anne M RoeslerY S Prakash
May 8, 2021·Pediatric Research·Catherine A MayerPeter M MacFarlane
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Gandhi F Pavón-RomeroLuis M Terán
Jun 26, 2021·Journal of Cellular Physiology·Sangeeta BhallamudiY S Prakash
Jun 15, 2021·International Immunopharmacology·Nandhine RajasekarSubbiah Rajasekaran

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Methods Mentioned

BETA
ELISA
zymography
bronchoalveolar lavage

Software Mentioned

Image Studio

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