Human alveolar epithelial cells type II are capable of TGFbeta-dependent epithelial-mesenchymal-transition and collagen-synthesis

BACKGROUND: The origin of collagen-producing cells in lung fibrosis is unclear. The involvement of embryonic signaling pathways has been acknowledged and trans-differentiation of epithelial cells is discussed critically. The work presented here investigates the role of TGFB in cytoskeleton remodeling and the expression of Epithelial-Mesenchymal-Transition markers by Alveolar Epithelial Cells Type II and tests the hypothesis if human alveolar epithelial cells are capable of trans-differentiation and production of pro-fibrotic collagen. METHODS: Primary human alveolar epithelial cells type II were extracted from donor tissues and stimulated with TGFbeta and a TGFbeta-inhibitor. Transcriptome and pathway analyses as well as validation of results on protein level were conducted. RESULTS: A TGFbeta-responsive fingerprint was found and investigated for mutual interactions. Interaction modules exhibited enrichment of genes that favor actin cytoskeleton remodeling, differentiation processes and collagen metabolism. Cross-validation of the TGFbeta-responsive fingerprint in an independent IPF dataset revealed overlap of genes and supported the direction of regulated genes and TGFbeta-specificity. CONCLUSIONS: Primary human alveolar epithelial cells type II seem undergo a TGFbeta-dependent phenotypic change, exhibit differential expression of EMT markers in vitro and acquire the potential to produce collagen.

• Goldmann, T.
• Zissel, G.
• Watz, H.
• Dromann, D.
• Reck, M.
• Kugler, C.
• Rabe, K. F.
• Marwitz, S.