Late Breaking Abstract - Calpain regulates epithelial-mesenchymal transition and its correlation with Akt signaling in pulmonary fibrosis.

Background: Epithelial-mesenchymal transition (EMT) is considered to play an important role in the pathogenesis of pulmonary fibrosis. Objective: The aim of the study was to investigate calpain how to regulate EMT and the signaling pathway in pulmonary fibrosis. Methods: Mice were treated with bleomycin (BLM) with or without calpeptin. HE staining and micro-CT were used to assess the fibrosis. PD150606, another calpain inhibitor, was performed in type II alveolar epithelial cells (AEC II) of mice. Cells were collected for western blot analysis after TGF-β1 treatment with or without PD150606. Results: Calpeptin could attenuate BLM-induced lung fibrosis (Fig 1a). EMT is a process which lose the epithelial marker E-cadherin (E-cad), and acquire the mesenchymal markers α-smooth muscle actin (α-SMA) and collagen-I. We found the expression of E-cad decreased, while the expression of α-SMA and collagen-I increased after BLM-treatment. Calpeptin could promote E-cad expression, while inhibit α-SMA and collagen-I expressions. Calpeptin also inhibited the phosphorylation of Akt, which is an important signaling associated with EMT (Fig 1b-c). Additionally, to further investigate calpain how to regulate EMT, AECII of mice were cultured successfully, which expressed surfactant protein C (SP-C) (Fig 2a). TGF-β1 can induce AEC II to undergo EMT with down-regulated E-cad expression, and up-regulated α-SMA and collagen-I expressions, while PD150606 could inhibit the process, as well as inhibit the phosphorylation of Akt (Fig 2b-c). Conclusion: Calpain inhibitor could attenuate BLM-induced lung fibrosis via suppressing the process of EMT and the activation of Akt signaling pathway.