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Toll-like receptor 5 tunes hepatic and pancreatic stellate cells activation
Objective: Stellate cells are responsible for liver and pancreas fibrosis and strictly correlate with tumourigenesis. Although their activation is reversible, an exacerbated signalling triggers chronic fibrosis. Toll-like receptors (TLRs) modulate stellate cells transition. TLR5 transduces the...
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| Autoren: | , , , , , , |
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| Format: | Artikel |
| Sprog: | engelsk |
| Udgivet: |
Philipps-Universität Marburg
2023
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| Fag: | |
| Online adgang: | PDF-Volltext |
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| Summary: | Objective: Stellate cells are responsible for liver
and pancreas fibrosis and strictly correlate with
tumourigenesis. Although their activation is reversible, an
exacerbated signalling triggers chronic fibrosis. Toll-like
receptors (TLRs) modulate stellate cells transition. TLR5
transduces the signal deriving by the binding to bacterial
flagellin from invading mobile bacteria.
Design: Human hepatic and pancreatic stellate cells
were activated by the administration of transforming
growth factor-beta
(TGF-β). TLR5 was transiently knocked
down by short-interference
RNA transfection. Reverse
Transcription-quantitativePCR
and western blot were
performed to analyse the transcript and protein level of
TLR5 and the transition players. Fluorescence microscopy
was performed to identify these targets in spheroids and
in the sections of murine fibrotic liver.
Results: TGF-β-activated human hepatic and pancreatic
stellate cells showed an increase of TLR5 expression.
TLR5 knockdown blocked the activation of those stellate
cells. Furthermore, TLR5 busted during murine liver
fibrosis and co-localised
with the inducible Collagen I.
Flagellin suppressed TLR5, COL1A1 and ACTA2 expression
after the administration of TGF-β. Instead, the antagonist
of TLR5 did not block the effect of TGF-β. Wortmannin, a
specific AKT inhibitor, induced TLR5 but not COL1A1 and
ACTA2 transcript and protein level.
Conclusion: TGF-β-mediated activation of hepatic and
pancreatic stellate cells requires the over-expression
of TLR5. Instead, its autonomous signalling inhibits the
activation of the stellate cells, thus prompting a signalling
through different regulatory pathways. |
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| Emne beskrivelse: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
| DOI: | 10.1136/bmjgast-2023-001148 |