Lipopolysaccharide induces retention of E-cadherin in the endoplasmic reticulum and promotes hybrid epithelial-to-mesenchymal transition of human embryonic stem cells-derived expandable lung epithelial cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F25%3A00082123" target="_blank" >RIV/65269705:_____/25:00082123 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00141553

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00011-025-02041-4" target="_blank" >https://link.springer.com/article/10.1007/s00011-025-02041-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00011-025-02041-4" target="_blank" >10.1007/s00011-025-02041-4</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lipopolysaccharide induces retention of E-cadherin in the endoplasmic reticulum and promotes hybrid epithelial-to-mesenchymal transition of human embryonic stem cells-derived expandable lung epithelial cells

Popis výsledku v původním jazyce

BackgroundLipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration.MethodsELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy.ResultsWe demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular beta-catenin level through retention of E-cadherin within the endoplasmic reticulum.ConclusionsHuman embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.

Název v anglickém jazyce

Lipopolysaccharide induces retention of E-cadherin in the endoplasmic reticulum and promotes hybrid epithelial-to-mesenchymal transition of human embryonic stem cells-derived expandable lung epithelial cells

Popis výsledku anglicky

BackgroundLipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration.MethodsELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy.ResultsWe demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular beta-catenin level through retention of E-cadherin within the endoplasmic reticulum.ConclusionsHuman embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/GA23-06675S" target="_blank" >GA23-06675S: Plicní stres a regenerace</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Inflammation Research

ISSN

1023-3830

e-ISSN

1420-908X

Svazek periodika

74

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

12

Strana od-do

82

Kód UT WoS článku

001493691400006

EID výsledku v databázi Scopus

2-s2.0-105005724865