PMID- 21651720
OWN - NLM
STAT- MEDLINE
DCOM- 20121026
LR  - 20220316
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 16
IP  - 4
DP  - 2012 Apr
TI  - Brain-derived neurotrophic factor induces proliferation of human airway smooth 
      muscle cells.
PG  - 812-23
LID - 10.1111/j.1582-4934.2011.01356.x [doi]
AB  - Airway diseases such as asthma involve increased airway smooth muscle (ASM) 
      contractility and remodelling via enhanced proliferation. Neurotrophins (NTs) 
      such as brain-derived neurotrophic factor (BDNF), well-known in the nervous 
      system, can regulate Ca(2+) signalling, and interact with cytokines in 
      contributing to airway hyperreactivity. In this study, we determined whether and 
      how BDNF regulates human ASM cell proliferation in the presence of inflammation, 
      thus testing its potential role in airway remodelling. Cells were treated with 10 
      nM BDNF, 25 ng/ml tumour necrosis factor (TNF-alpha) or interleukin-13 (IL-13), or 10 
      ng/ml platelet-derived growth factor (PDGF). Proliferation was measured using 
      CyQuant dye, with immunoblotting of cell cycle proteins predicted to change with 
      proliferation. Forty-eight hours of BDNF enhanced ASM proliferation to  approximately  50% of 
      that by PDGF or cytokines. Transfection with small interfering RNAs (siRNAs) 
      targeting high-affinity tropomyosin-related kinase B receptor abolished BDNF 
      effects on proliferation, whereas low-affinity 75 kD neurotrophin receptor 
      (p75NTR) siRNA had no effect. Systematic pharmacologic inhibition of different 
      components of ERK1/2 and PI3K/Akt1 pathways blunted BDNF or TNF-alpha-induced 
      proliferation. BDNF also induced IkappaB phosphorylation and nuclear translocation of 
      p50 and p65 NF-kappaB subunits, with electron mobility shift assay confirmation of 
      NF-kappaB binding to consensus DNA sequence. These results demonstrate that NTs such 
      as BDNF can enhance human ASM cell proliferation by activating 
      proliferation-specific signalling pathways and a versatile transcription factor 
      such as NF-kappaB, which are common to cytokines and growth factors involved in 
      asthma.
CI  - (c) 2011 The Authors Journal of Cellular and Molecular Medicine (c) 2011 Foundation 
      for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
FAU - Aravamudan, Bharathi
AU  - Aravamudan B
AD  - Department of Anesthesiology, College of Medicine, Mayo Clinic, Rochester, MN 
      55905, USA.
FAU - Thompson, Michael
AU  - Thompson M
FAU - Pabelick, Christina
AU  - Pabelick C
FAU - Prakash, Y S
AU  - Prakash YS
LA  - eng
GR  - R01 HL056470-11/HL/NHLBI NIH HHS/United States
GR  - HL088029/HL/NHLBI NIH HHS/United States
GR  - R01 HL090595/HL/NHLBI NIH HHS/United States
GR  - HL56470/HL/NHLBI NIH HHS/United States
GR  - R01 HL056470/HL/NHLBI NIH HHS/United States
GR  - R01 HL090595-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL088029/HL/NHLBI NIH HHS/United States
GR  - R01 HL090595-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL088029-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL088029-02/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Interleukin-13)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Bronchi/cytology/*drug effects
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Electrophoretic Mobility Shift Assay
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-13/pharmacology
MH  - Muscle, Smooth/cytology/*drug effects
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC3175295
MID - NIHMS302518
EDAT- 2011/06/10 06:00
MHDA- 2012/10/27 06:00
PMCR- 2012/04/01
CRDT- 2011/06/10 06:00
PHST- 2011/06/10 06:00 [entrez]
PHST- 2011/06/10 06:00 [pubmed]
PHST- 2012/10/27 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - 10.1111/j.1582-4934.2011.01356.x [doi]
PST - ppublish
SO  - J Cell Mol Med. 2012 Apr;16(4):812-23. doi: 10.1111/j.1582-4934.2011.01356.x.