期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/ijms22010225
关键词
5-HT; 5-HT2B receptor antagonism; fibrosis; ILD
资金
- Swedish Research Council in Medicine and Health [11550, 2016-01190]
- Swedish Heart-Lung Foundation [20140293, 20130507, 20200847]
- Swedish foundation for Strategic Research [SBE13-0130]
- Royal Physiographic Society of Lund
- Olle Engkvist Foun-dation
- Crafoord Foundation
- Greta and John Kock Foundation
- Alfred Osterlund Foundation
- Ake och Inger Bergkvist foundation
- Medical Faculty of Lund University
- ALF (Region Skane)
- Lund University
- Swedish Research Council in VR3R project [2016-01190]
- Swedish Foundation for Strategic Research (SSF) [SBE13-0130] Funding Source: Swedish Foundation for Strategic Research (SSF)
- Swedish Research Council [2016-01190] Funding Source: Swedish Research Council
Although PF-ILDs have different etiology and histopathological patterns, they share similarities in disease mechanisms, suggesting common pathogenetic pathways.
Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 conditions, 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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