In summary, we found that IPF fibroblasts utilize the PTEN/Akt/mTOR-dependent autophagic regulatory pathway to elude the cell death inducing effect of polymerized collagen, and the alteration of the PTEN/Akt axis and the inhibition of autophagic activity may be an effective approach to sensitize IPF fibroblasts to collagen matrix and a useful strategy to limit the progression of IPF. This evidence concerns the gene PTEN and idiopathic pulmonary fibrosis.