Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition
Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition
About this item
Full title
Author / Creator
Wasnick, Roxana M , Korfei, Martina , Piskulak, Katarzyna , Henneke, Ingrid , Wilhelm, Jochen , Mahavadi, Poornima , Von Der Beck, Daniel , Koch, Miriam , Shalashova, Irina , Klymenko, Oleksiy , Fink, Ludger , Witt, Heiko , Hackstein, Holger , Elie El Agha , Bellusci, Saverio , Klepetko, Walter , Koenigshoff, Melanie , Eickelberg, Oliver , Braun, Thomas , Seeger, Werner , Ruppert, Clemens and Guenther, Andreas
Publisher
Cold Spring Harbor: Cold Spring Harbor Laboratory Press
Journal title
Language
English
Formats
Publication information
Publisher
Cold Spring Harbor: Cold Spring Harbor Laboratory Press
Subjects
More information
Scope and Contents
Contents
Alveolar epithelial cell type II (AEC2) injury underlies idiopathic pulmonary fibrosis (IPF). Here we show increased Notch1 signaling in AEC2s in human IPF and IPF models, causing enhanced proliferation and de-differentiation of AEC2s. As a result, we observed defective surfactant protein (SP)-B/C processing, elevated alveolar surface tension, repetitive alveolar collapse and development of lung fibrosis. Similar changes were encountered upon pharmacological inhibition of SP-B/C processing in vivo by pepstatin A. Inhibition of Notch signaling in cultured human IPF precision cut lung slices improved surfactant processing capacity of AEC2s and reversed fibrosis. Notch1 therefore offers as novel therapeutic target. Footnotes * https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE95856 * https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68239...
Alternative Titles
Full title
Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition
Authors, Artists and Contributors
Author / Creator
Korfei, Martina
Piskulak, Katarzyna
Henneke, Ingrid
Wilhelm, Jochen
Mahavadi, Poornima
Von Der Beck, Daniel
Koch, Miriam
Shalashova, Irina
Klymenko, Oleksiy
Fink, Ludger
Witt, Heiko
Hackstein, Holger
Elie El Agha
Bellusci, Saverio
Klepetko, Walter
Koenigshoff, Melanie
Eickelberg, Oliver
Braun, Thomas
Seeger, Werner
Ruppert, Clemens
Guenther, Andreas
Identifiers
Primary Identifiers
Record Identifier
TN_cdi_proquest_journals_2192787076
Permalink
https://devfeature-collection.sl.nsw.gov.au/record/TN_cdi_proquest_journals_2192787076
Other Identifiers
E-ISSN
2692-8205
DOI
10.1101/580498
How to access this item
https://www.proquest.com/docview/2192787076?pq-origsite=primo&accountid=13902
