Proposed model for the desensitization to polymerized collagen induced cell death in IPF fibroblasts.

<p>We previously found that when control fibroblasts are attached to polymerized collagen, cell death is increased <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094616#pone.0094616-Nho2" target="_blank">[44]</a>. In contrast, IPF fibroblasts are resistant to collagen matrix induced cell death. In this study, we further elucidate the underlying mechanism that bestows a highly viable IPF fibroblast phenotype in response to polymerized collagen. When IPF fibroblasts are allowed to interact with collagen matrix, Akt activity is inappropriately high due to PTEN suppression, which in turn increases mTOR kinase activity. Autophagy in IPF fibroblasts is then subsequently suppressed, and this pathological event desensitizes IPF fibroblasts to polymerized collagen induced cell death. Upwards arrow indicates enhanced activity. Downwards arrow indicates reduced activity.