Activation of M2 macrophages in the lung is regarded to be a crucial component in increasing lung fibrosis, and it was discovered that Shh increases the secretion of osteopontin in macrophages via the Shh/Gli signaling cascade, and the secreted osteopontin act on surrounding macrophages in an autocrine or paracrine manner and induce macrophage M2 polarization via the JAK2/STAT3 signaling pathway, which may ultimately promote the progression of pulmonary fibrosis by affecting the activation and proliferation of fibroblasts and the production of pro-fibrotic cytokines (113). This evidence concerns the gene SPP1 and pulmonary fibrosis.