PMID- 28522569
OWN - NLM
STAT- MEDLINE
DCOM- 20170829
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 313
IP  - 2
DP  - 2017 Aug 1
TI  - Brain-derived neurotrophic factor and airway fibrosis in asthma.
PG  - L360-L370
LID - 10.1152/ajplung.00580.2016 [doi]
AB  - 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 TNFalpha significantly increased BDNF 
      secretion, particularly in asthmatic ASM, whereas no significant changes were 
      observed with IL-13. Chelation of BDNF using TrkB-Fc reversed TNFalpha-induced 
      increase in ECM deposition. Conditioned media from asthmatic ASM enhanced ECM 
      generation in nonasthmatic ASM, which was blunted by BDNF chelation. 
      Inflammation-induced changes in MMP-2, MMP-9, and tissue inhibitor 
      metalloproteinases (TIMP-1, TIMP-2) were reversed in the presence of TrkB-Fc. 
      These novel data suggest ASM as an inflammation-sensitive source of BDNF within 
      human airways, with autocrine effects on fibrosis relevant to asthma.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Freeman, Michelle R
AU  - Freeman MR
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Sathish, Venkatachalem
AU  - Sathish V
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, 
      Minnesota; and.
FAU - Manlove, Logan
AU  - Manlove L
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Wang, Shengyu
AU  - Wang S
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
AD  - Department of Respiratory Medicine, First Affiliated Hospital of Xi'an Medical 
      University, Xi'an, Shaanxi, People's Republic of China.
FAU - Britt, Rodney D Jr
AU  - Britt RD Jr
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Thompson, Michael A
AU  - Thompson MA
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Pabelick, Christina M
AU  - Pabelick CM
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota.
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, 
      Minnesota; and.
FAU - Prakash, Y S
AU  - Prakash YS
AUID- ORCID: 0000-0002-2968-224X
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      Minnesota; prakash.ys@mayo.edu.
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, 
      Minnesota; and.
LA  - eng
GR  - R01 HL056470/HL/NHLBI NIH HHS/United States
GR  - R01 HL088029/HL/NHLBI NIH HHS/United States
GR  - R01 HL123494/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20170518
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type III)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-13)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Airway Remodeling/*physiology
MH  - Asthma/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Collagen Type I/metabolism
MH  - Collagen Type III/metabolism
MH  - Cytokines/metabolism
MH  - Fibrosis/*metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interleukin-13/metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Muscle, Smooth/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - Respiratory System/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC5582935
OTO - NOTNLM
OT  - airway smooth muscle
OT  - collagen
OT  - extracellular matrix
OT  - neurotrophin
OT  - tropomyosin-related kinase
EDAT- 2017/05/20 06:00
MHDA- 2017/08/30 06:00
PMCR- 2018/08/01
CRDT- 2017/05/20 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/04/17 00:00 [revised]
PHST- 2017/05/11 00:00 [accepted]
PHST- 2017/05/20 06:00 [pubmed]
PHST- 2017/08/30 06:00 [medline]
PHST- 2017/05/20 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - ajplung.00580.2016 [pii]
AID - L-00580-2016 [pii]
AID - 10.1152/ajplung.00580.2016 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2017 Aug 1;313(2):L360-L370. doi: 
      10.1152/ajplung.00580.2016. Epub 2017 May 18.