Emerging role of BMPs/BMPR2 signaling pathway in treatment for pulmonary fibrosis

Biomed Pharmacother. 2024 Sep:178:117178. doi: 10.1016/j.biopha.2024.117178. Epub 2024 Aug 13.

Abstract

Pulmonary fibrosis is a fatal and chronic lung disease that is characterized by accumulation of thickened scar in the lungs and impairment of gas exchange. The cases with unknown etiology are referred as idiopathic pulmonary fibrosis (IPF). There are currently no effective therapeutics to cure the disease; thus, the investigation of the pathogenesis of IPF is of great importance. Recent studies on bone morphogenic proteins (BMPs) and their receptors have indicated that reduction of BMP signaling in lungs may play a significant role in the development of lung fibrosis. BMPs are members of TGF-β superfamily, and they have been shown to play an anti-fibrotic role in combating TGF-β-mediated pathways. The impact of BMP receptors, in particular BMPR2, on pulmonary fibrosis is growing attraction to researchers. Previous studies on BMPR2 have often focused on pulmonary arterial hypertension (PAH). Given the strong clinical association between PAH and lung fibrosis, understanding BMPs/BMPR2-mediated signaling pathway is important for development of therapeutic strategies to treat IPF. In this review, we comprehensively review recent studies regarding the biological functions of BMPs and their receptors in lungs, especially focusing on their roles in the pathogenesis of pulmonary fibrosis and fibrosis resolution.

Keywords: Anti-fibrosis; BMP ligands; BMP receptors; Myofibroblast differentiation; Pro-fibrotic responses; Pulmonary fibrosis; TGF-β pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Antifibrotic Agents / pharmacology
  • Antifibrotic Agents / therapeutic use
  • Bone Morphogenetic Protein Receptors, Type II* / metabolism
  • Bone Morphogenetic Proteins* / metabolism
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / metabolism
  • Pulmonary Fibrosis* / pathology
  • Signal Transduction*

Substances

  • Bone Morphogenetic Protein Receptors, Type II
  • Bone Morphogenetic Proteins
  • BMPR2 protein, human
  • Antifibrotic Agents