Pathological Insight into 5-HT 2B Receptor Activation in Fibrosing Interstitial Lung Diseases

Int J Mol Sci. 2020 Dec 28;22(1):225. doi: 10.3390/ijms22010225.

Abstract

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.

Keywords: 5-HT; 5-HT2B receptor antagonism; ILD; fibrosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Idiopathic Pulmonary Fibrosis / immunology
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Inflammation / pathology
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / metabolism*
  • Lung Diseases, Interstitial / pathology*
  • Models, Biological
  • Receptor, Serotonin, 5-HT2B / metabolism*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology

Substances

  • Receptor, Serotonin, 5-HT2B
  • Serotonin 5-HT2 Receptor Antagonists