Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma

Rodney Jr. Britt, Michael A. Thompson, Sarah A. Wicher, Logan J. Manlove, Anne Roesler, Yun Hua Fang, Carolyn Roos, Leslie Smith, Jordan D Miller, Christina M Pabelick, Y.s. Prakash

Research output: Contribution to journalArticle

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Abstract

Recent studies have demonstrated an effect of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), on airway contractility [ via increased airway smooth muscle (ASM) intracellular calcium [Ca2+]i] and remodeling (ASM proliferation and extracellular matrix formation) in the context of airway disease. In the present study, we examined the role of BDNF in allergen-induced airway inflammation using 2 transgenic models: 1) tropomyosin-related kinase B (TrkB) conditional knockin (TrkBKI) mice allowing for inducible, reversible disruption of BDNF receptor kinase activity by administration of 1NMPP1, a PP1 derivative, and 2) smooth muscle-specific BDNF knockout (BDNFfl/fl/SMMHC11Cre/0) mice. Adult mice were intranasally challenged with PBS or mixed allergen ( Alternaria alternata, Aspergillus fumigatus, house dust mite, and ovalbumin) for 4 wk. Our data show that administration of 1NMPP1 in TrkBKI mice during the 4-wk allergen challenge blunted airway hyperresponsiveness (AHR) and reduced fibronectin mRNA expression in ASM layers but did not reduce inflammation per se. Smooth muscle-specific deletion of BDNF reduced AHR and blunted airway fibrosis but did not significantly alter airway inflammation. Together, our novel data indicate that TrkB signaling is a key modulator of AHR and that smooth muscle-derived BDNF mediates these effects during allergic airway inflammation.-Britt, R. D., Jr., Thompson, M. A., Wicher, S. A., Manlove, L. J., Roesler, A., Fang, Y.-H., Roos, C., Smith, L., Miller, J. D., Pabelick, C. M., Prakash, Y. S. Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma.

Original languageEnglish (US)
Pages (from-to)3024-3034
Number of pages11
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Brain-Derived Neurotrophic Factor
Smooth Muscle
Muscle
Asthma
Allergens
Inflammation
trkB Receptor
Airway Remodeling
Tropomyosin
Phosphotransferases
Alternaria
Pyroglyphidae
Aspergillus fumigatus
Ovalbumin
Nerve Growth Factors
Fibronectins
Extracellular Matrix
Fibrosis
Calcium
Messenger RNA

Keywords

  • extracellular matrix
  • fibrosis
  • neurotrophin
  • TrkB

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma. / Britt, Rodney Jr.; Thompson, Michael A.; Wicher, Sarah A.; Manlove, Logan J.; Roesler, Anne; Fang, Yun Hua; Roos, Carolyn; Smith, Leslie; Miller, Jordan D; Pabelick, Christina M; Prakash, Y.s.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 2, 01.02.2019, p. 3024-3034.

Research output: Contribution to journalArticle

Britt, Rodney Jr. ; Thompson, Michael A. ; Wicher, Sarah A. ; Manlove, Logan J. ; Roesler, Anne ; Fang, Yun Hua ; Roos, Carolyn ; Smith, Leslie ; Miller, Jordan D ; Pabelick, Christina M ; Prakash, Y.s. / Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 2. pp. 3024-3034.
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