Deritei2026 - SHH-driven EMT in COPD wound healing

ABSTRACT: We modeled the effects of altered Hedgehog signaling on the behavior of lung epithelial cells during the wounding of a cellular monolayer by examining the interplay between EMT, mechanosensing, and proliferation in response to icroenvironmental signals near the wound. To do this, we expanded a previously published model of mechanosensitive EMT (MODEL2312140001), which examined the synergistic effect of low cell density, stiff extracellular matrix (ECM), and strong mitogens in driving EMT in the absence of transforming signals such as TGFβ. The current expanded model includes a detailed cell cycle control circuit driven by growth signaling, integrated with adhesion, contact inhibition, control of EMT by TGFβ or growth signals, migration, as well as apoptosis. We added a Hedgehog signaling module such that it impacts the rest of the network by promoting EMT and survival. The rest of the network, in turn, modulates the SHH signal primarily via C/ EBPα, a transcription factor required for lung maturation and known to reduce GLI1 expression in lung epithelia. To model the effect of EMT on the underlying ECM, we incorporated the feedback control of key lung alveolar ECM components by matrix metalloproteinases MMP2/7/9. These MMPs lead to basement membrane destruction and interstitial ECM stiffening during EMT.

SUBMITTER: Erzsébet Ravasz Regan  

PROVIDER: MODEL2605070001 | BioModels | 2026-07-25

REPOSITORIES: BioModels