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  3. Medizin - Open Access LMU - Teil 17/22 Podcast
  4. Increased expression of 5-hydroxytryptamine(2A/B) receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention
Background Idiopathic pulmonary fibrosis (IPF) has a poor prognosis
and limited responsiveness to available treatments. It is
characterised by epithelial cell injury, fibroblast activation and
proliferation and extracellular matrix deposition. Serotonin
(5-hydroxytryptamine; 5-HT) induces fibroblast proliferation via
the 5-HTR2A and 5-HTR2B receptors, but its pathophysiological role
in IPF remains unclear. A study was undertaken to determine the
expression of 5-HT receptors in IPF and experimental lung fibrosis
and to investigate the effects of therapeutic inhibition of
5-HTR2A/B signalling on lung fibrosis in vivo and in vitro. Methods
and results Quantitative RT-PCR showed that the expression of
5-HTR1A/B and 5-HTR2B was significantly increased in the lungs of
patients with IPF (n = 12) and in those with non-specific
interstitial pneumonia (NSIP, n = 6) compared with transplant
donors (n = 12). The expression of 5-HTR2A was increased
specifically in IPF lungs but not in NSIP lungs. While 5-HTR2A
protein largely localised to fibroblasts, 5-HTR2B localised to the
epithelium. To assess the effects of 5HTR(2A/B) inhibition on
fibrogenesis in vivo, mice were subjected to bleomycin-induced lung
fibrosis and treated with the 5-HTR2A/B antagonist terguride (or
vehicle) in a therapeutic approach (days 14-28 after bleomycin).
Terguride-treated mice had significantly improved lung function and
histology and decreased collagen content compared with
vehicle-treated mice. Functional in vitro studies showed that
terguride is a potent inhibitor of transforming growth factor
beta(1)- or WNT3a-induced collagen production. Conclusion The
studies revealed an increased expression of 5-HTR2A specifically in
IPF. Blockade of 5-HTR2A/B signalling by terguride reversed lung
fibrosis and is thus a promising therapeutic approach for IPF.

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„Increased expression of 5-hydroxytryptamine(2A/B) receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention“

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