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

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Respiratory research. - 19 (2018) , 138, ISSN: 1465-993X

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2019
Urheber
Beteiligte Personen und Organisationen

DOI
10.1186/s12931-018-0841-9
URN
urn:nbn:de:bsz:25-freidok-1481715
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:47 MEZ

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Beteiligte

Entstanden

  • 2019

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