Gene expression profile of intestinal organoids from people with cystic fibrosis upon exposure to elexacaftor/tezacaftor/ivacaftor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F25%3A10485713" target="_blank" >RIV/00216208:11130/25:10485713 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/25:10485713

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gM5g9HQJAN" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gM5g9HQJAN</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jcf.2024.09.005" target="_blank" >10.1016/j.jcf.2024.09.005</a>

Result language

angličtina

Original language name

Gene expression profile of intestinal organoids from people with cystic fibrosis upon exposure to elexacaftor/tezacaftor/ivacaftor

Original language description

The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h. Gene expression was assessed using 3&apos;-mRNA sequencing and modelled using negative binomial models. Incubation with ETI resulted in a significant upregulation of several biological processes: mostly related to chemokines and signalling, chemotaxis, and tissue development processes. No changes were observed in abundance of the CFTR transcripts or in CFTR-related gene sets and pathways. The genes and pathways associated with ETI did not overlap with those whose expression changed with time only. PDIOs with a high FIS response did not significantly differ in any interpretable gene from the FIS-low organoids. The changes in the PDIOs gene expression upon the exposure to ETI cannot explain differences in the magnitude of PDIOs FIS-measured response to ETI. In conclusion, on incubation with ETI, genes of the CFTR-related pathways do not change their transcriptional activity; instead, overexpression was observed in genes of inflammatory-like cytokine response and receptor activation pathways.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30303 - Infectious Diseases

Project

<a href="/en/project/NU23-07-00079" target="_blank" >NU23-07-00079: Optimization of cystic fibrosis patient-derived cellular models to asses restoration of CFTR function in patients with cystic fibrosis</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

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

Name of the periodical

Journal of Cystic Fibrosis

ISSN

1569-1993

e-ISSN

1873-5010

Volume of the periodical

24

Issue of the periodical within the volume

1

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

7

Pages from-to

157-163

UT code for WoS article

001422297200001

EID of the result in the Scopus database

2-s2.0-85203799685