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

Figure 2

Cellular responses induced by IGF signaling pathway in pulmonary fibrosis. IGF-1 is produced by alveolar macrophages (AMs) and fibroblasts. IGF-1 activates fibroblast via PI3K/Akt and MAPK signaling and leads to fibroblast-myofibroblast transition via PI3K/Akt, MAPK, EGR1/2, and FOS signaling. Transition of type II alveolar epithelial cells to fibroblast-like cells is mediated by IGF-1-induced ERK activation. IGF-1 mediates alternative activation of alveolar macrophages, generating type 2-activated macrophages. Except for fibroblasts and myofibroblasts, EMT-generated fibroblast-like cells and alternative type 2-activated macrophages are all capable of producing extracellular matrix (ECM) and profibrotic signals.