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

Rodney D. 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 journalArticlepeer-review

8 Scopus citations

Abstract

Recent studies have demonstrated an effect of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), on airway contractility [via increased airway smoothmuscle (ASM)intracellular calcium[Ca2+]i] and remodeling (ASMproliferation and extracellularmatrix 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 fibronectinmRNA expression in ASMlayers but did not reduce inflammation per se.Smoothmuscle-specific deletion ofBDNFreducedAHRandbluntedairway fibrosisbut didnot significantly alter airway inflammation.Together, ournovel data indicate thatTrkBsignaling is a keymodulator ofAHRand that smooth muscle-derived BDNF mediates these effects during allergic airway inflammation.

Original languageEnglish (US)
Pages (from-to)3024-3034
Number of pages11
JournalFASEB Journal
Volume33
Issue number2
DOIs
StatePublished - 2019

Keywords

  • Extracellular matrix
  • Fibrosis
  • Neurotrophin
  • TrkB

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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