Targeting insulin-like growth factor-I and insulin-like growth factor-binding
protein-3 signaling pathways A novel therapeutic approach for asthma
#MMPMID24219511
Lee H
; Kim SR
; Oh Y
; Cho SH
; Schleimer RP
; Lee YC
Am J Respir Cell Mol Biol
2014[Apr]; 50
(4
): 667-77
PMID24219511
show ga
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-?B 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.
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