Insulin-Like Growth Factor-1 Signaling in Lung Development and Inflammatory Lung Diseases

Abstract

Insulin-like growth factor-1 (IGF-1) was firstly identified as a hormone that mediates the biological effects of growth hormone. Accumulating data have indicated the role of IGF-1 signaling pathway in lung development and diseases such as congenital disorders, cancers, inflammation, and fibrosis. IGF-1 signaling modulates the development and differentiation of many types of lung cells, including airway basal cells, club cells, alveolar epithelial cells, and fibroblasts. IGF-1 signaling deficiency results in alveolar hyperplasia in humans and disrupted lung architecture in animal models. The components of IGF-1 signaling pathways are potentiated as biomarkers as they are dysregulated locally or systemically in lung diseases, whereas data may be inconsistent or even paradoxical among different studies. The usage of IGF-1-based therapeutic agents urges for more researches in developmental disorders and inflammatory lung diseases, as the majority of current data are collected from limited number of animal experiments and are generally less exuberant than those in lung cancer. Elucidation of these questions by further bench-to-bedside researches may provide us with rational clinical diagnostic approaches and agents concerning IGF-1 signaling in lung diseases.

Questioning Cause and Effect: Children with Severe Asthma Exhibit High Levels of Inflammatory Biomarkers Including Beta-Hexosaminidase, but Low Levels of Vitamin A and Immunoglobulins

“…One highly significant finding in our study was that severe asthmatics had reduced IGFBP-1, a permissive condition for increased free IGF-1, both in comparison to hospitalized nonasthmatics and healthy children. This finding, together with previous reports of IGF-1 involvement in asthma pathogenesis [ 62 , 63 ] suggest that IGF-1 may provide an important target for asthma therapy.…”

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

“…When respiratory muscles are impacted by COPD, skeletal muscle wasting or cachexia often develops, in which insulin-like growth factor 1 (IGF-1) signaling plays a major role in promoting disease onset and progression, resulting from the activation of the mTOR signaling pathway [191][192][193][194]. The severity of COPD has been linked to significantly low levels of IGF-1 in serum, with cachectic COPD patients showing decreased protein levels of IGF-1 in muscle [195][196][197][198].…”

A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice

“…mRNA and protein levels of IGF1R have been previously shown to correlate in various tissues, including the lung. [80][81][82] Human and murine fetal lung development is crucially driven by IGF1/IGF1R signaling, which promotes vascular and epithelial differentiation as well as alveolarization. [83][84][85][86] Our results and those of others have shown a steadily increasing Igf1 and Igf1r expression throughout prenatal life in nonstressed murine offspring.…”