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Pathological insight into 5-ht2b receptor activation in fibrosing interstitial lung diseases

Löfdahl, Anna LU ; Tornling, Göran ; Wigén, Jenny LU ; Larsson-Callerfelt, Anna Karin LU orcid ; Wenglén, Christina LU and Westergren-Thorsson, Gunilla LU orcid (2021) In International Journal of Molecular Sciences 22(1).
Abstract

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 con-ditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)2 receptors have been implicated to have important roles... (More)

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 con-ditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)2 receptors have been implicated to have important roles in observed profibrotic actions. Our research findings in support by others, demonstrate antifibrotic effects with 5-HT2B receptor antagonists, alleviating several key events common for the fibrotic diseases such as myofibroblast differentiation and connective tissue deposition. In this review, we will address the potential role of 5-HT and in particular the 5-HT2B receptors in three PF-ILDs: ILD associated with systemic sclerosis (SSc-ILD), ILD associated with rheumatoid arthritis (RA-ILD) and IPF. Highlighting the converging pathways in these diseases discloses the 5-HT2B receptor as a potential disease target for PF-ILDs, which today have an urgent unmet need for therapeutic strategies.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
5-HT, 5-HT receptor antagonism, Fibrosis, ILD
in
International Journal of Molecular Sciences
volume
22
issue
1
article number
225
pages
19 pages
publisher
MDPI AG
external identifiers
  • scopus:85098548371
  • pmid:33379351
ISSN
1661-6596
DOI
10.3390/ijms22010225
language
English
LU publication?
yes
id
b4763473-83d0-4d56-baa8-9e74ad0f0262
date added to LUP
2021-01-13 12:56:33
date last changed
2024-06-13 04:59:12
@article{b4763473-83d0-4d56-baa8-9e74ad0f0262,
  abstract     = {{<p>Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 con-ditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)<sub>2</sub> receptors have been implicated to have important roles in observed profibrotic actions. Our research findings in support by others, demonstrate antifibrotic effects with 5-HT<sub>2B</sub> receptor antagonists, alleviating several key events common for the fibrotic diseases such as myofibroblast differentiation and connective tissue deposition. In this review, we will address the potential role of 5-HT and in particular the 5-HT<sub>2B</sub> receptors in three PF-ILDs: ILD associated with systemic sclerosis (SSc-ILD), ILD associated with rheumatoid arthritis (RA-ILD) and IPF. Highlighting the converging pathways in these diseases discloses the 5-HT<sub>2B</sub> receptor as a potential disease target for PF-ILDs, which today have an urgent unmet need for therapeutic strategies.</p>}},
  author       = {{Löfdahl, Anna and Tornling, Göran and Wigén, Jenny and Larsson-Callerfelt, Anna Karin and Wenglén, Christina and Westergren-Thorsson, Gunilla}},
  issn         = {{1661-6596}},
  keywords     = {{5-HT; 5-HT receptor antagonism; Fibrosis; ILD}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Pathological insight into 5-ht<sub>2b</sub> receptor activation in fibrosing interstitial lung diseases}},
  url          = {{http://dx.doi.org/10.3390/ijms22010225}},
  doi          = {{10.3390/ijms22010225}},
  volume       = {{22}},
  year         = {{2021}},
}