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

Torsten Goldmann, Gernot Zissel, Henrik Watz, Daniel Drömann, Martin Reck, Christian Kugler, Klaus F. Rabe, Sebastian Marwitz*

*Corresponding author for this work
18 Citations (Scopus)

Abstract

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 TGFβ and a TGFβ-inhibitor. Transcriptome and pathway analyses as well as validation of results on protein level were conducted. Results: A TGFβ-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 TGFβ-responsive fingerprint in an independent IPF dataset revealed overlap of genes and supported the direction of regulated genes and TGFβ-specificity. Conclusions: Primary human alveolar epithelial cells type II seem undergo a TGFβ-dependent phenotypic change, exhibit differential expression of EMT markers in vitro and acquire the potential to produce collagen.

Original languageEnglish
Article number138
JournalRespiratory Research
Volume19
Issue number1
ISSN1465-9921
DOIs
Publication statusPublished - 24.07.2018

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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