Targeting insulin-like growth factor-I and insulin-like growth factor-binding protein-3 signaling pathways: A novel therapeutic approach for asthma

Hyun Lee, So Ri Kim, Youngman Oh, Seong Ho Cho, Robert P. Schleimer, Yong Chul Lee*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations

Abstract

Insulin-like growth factor (IGF)-I has been recognized to play critical roles in the pathogenesis of asthma, whereas IGF-binding protein (IGFBP)-3 blocks crucial physiologic manifestations of asthma. IGF-I enhances subepithelial fibrosis, airway inflammation, airway hyperresponsiveness, and airway smooth muscle hyperplasia by interacting with various inflammatory mediators and complex signaling pathways, such as intercellular adhesion molecule-1, and the hypoxia-inducible factor/vascular endothelial growth factor axis. On the other hand, IGFBP-3 decreases airway inflammation and airway hyperresponsiveness through IGFBP-3 receptor-mediated activation of caspases, which subsequently inhibits NF-κB signaling pathway. It also inhibits the IGF-I/hypoxia-inducible factor/vascular endothelial growth factor axis via IGF-I-dependent and/or IGF-I-independent mechanisms. This Translational Review summarizes the role of IGF-I and IGFBP-3 in the context of allergic airway disease, and discusses the therapeutic potential of various strategies targeting the IGF-I and IGFBP-3 signaling pathways for the management of asthma.

Original languageEnglish (US)
Pages (from-to)667-677
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume50
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Asthma
  • Insulin-like growth factor-I
  • Insulin-like growth factor-binding protein-3

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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