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Human alveolar epithelial cells type II are capable of TGFβ-dependent epithelial-mesenchymal-transition and collagen-synthesis
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Human alveolar epithelial cells type II are capable of TGFβ-dependent epithelial-mesenchymal-transition and collagen-synthesis
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Journal Article
Human alveolar epithelial cells type II are capable of TGFβ-dependent epithelial-mesenchymal-transition and collagen-synthesis
2018
Overview
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.
Publisher
BioMed Central,Nature Publishing Group,BMC
Subject
/ Aged
/ Alveolar Epithelial Cells - drug effects
/ Alveolar Epithelial Cells - metabolism
/ Alveoli
/ Cloning
/ Collagen
/ Embryos
/ EMT
/ Epithelial-Mesenchymal Transition - drug effects
/ Epithelial-Mesenchymal Transition - physiology
/ Female
/ Fibrosis
/ Genes
/ Humans
/ Kinases
/ Male
/ Markers
/ Medicine
/ Pneumology/Respiratory System
/ Proteins
