Using an in vivo bleomycin mouse model, we have found that high-tidal-volume ventilation increased pulmonary fibrosis by biochemical analysis of hydroxyproline, Masson trichrome staining of collagen, immunohistochemical staining for fibroblasts, microvascular permeability, and production of MIP-2, but not IP-10 production, which was, at least in part, dependent, on the Akt and ERK1/2 pathways (Figure 9). This evidence concerns the gene MAPK3 and pulmonary fibrosis.