Role of Insulin-like Growth Factor Binding Protein-3 in Allergic Airway Remodeling

Insulin-like Growth Factor-binding Protein-3 (IGFBP-3) Blocks the Effects of Asthma by Negatively Regulating NF-κB Signaling through IGFBP-3R-mediated Activation of Caspases

“…Furthermore, it has been reported that IGF-I plays an important role in the late stage of inflammation and remodeling of the asthmatic airway (41), and IGFBP-3 may modulate the biological effects of IGF-I in allergic airway remodeling in humans (42). Thus, these studies support our findings and provide evidence for relevance to asthma in humans.…”

Lung Pericytes and Resident Fibroblasts

“…Moreover, IGF binding proteins and connective tissue growth factor are important modulators of key pathways for lung development, including WNT, PDGF, and TGFb. 12,30,77 Thus, the gene expression profiles imply that in the mature organ these Col1 þ populations are still operating much of the developmental program used to generate the lung, most plausibly in maintenance and repair.…”

Targeting Insulin-Like Growth Factor-I and Insulin-Like Growth Factor–Binding Protein-3 Signaling Pathways. A Novel Therapeutic Approach for Asthma

“…Conversely, IGFBPs can inhibit the actions of IGFs, because IGFs bind with higher affinity to IGFBPs than the IGF-IR, thereby reducing IGF bioavailability (38). Second, IGFBPs can also exert their own intrinsic biological roles, independent of IGFs (IGFindependent action of IGFBPs) (10, 39), including anti-(8, 9) or proinflammatory (7), anti- (40,41) or proangiogenic (40,42,43), or profibrotic responses (7,44). Among them, IGFBP-3 is a well documented inhibitor of cell growth and/or promoter of apoptosis.…”

“…Thus, regulation of the IGF-I signaling pathway might have therapeutic potential (4)(5)(6). On the other hand, recent studies have also shown that IGF-binding protein (IGFBP)-3 plays a critical role in inflammatory responses through IGF-I-dependent and/or IGF-I-independent mechanisms (7)(8)(9).…”