Galectin-3 participates in PASMC migration and proliferation by interacting with TGF-β1

Life Sci. 2021 Jun 1:274:119347. doi: 10.1016/j.lfs.2021.119347. Epub 2021 Mar 11.

Abstract

Pulmonary vascular remodelling is one of the most important factors for pulmonary hypertension (PH). Galectin-3 (Gal-3) is a β-galactoside-binding lectin. In the latest literature, Gal-3 has been reported to be involved in pulmonary vascular remodelling, and its underlying mechanism is unclear. Our research aims to prove the effect of Gal-3 on the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMC) induced by transforming growth factor β1 (TGF-β1) and to study its mechanism. In vivo experiment: In Sprague-Dawley (SD) rats, monocrotaline was injected intraperitoneally to establish a PH model, and the Gal-3 inhibitor (modified citrus pectin, MCP) 28 Ds was administered in the stomach. The results indicate that Gal-3 and TGF-β1 may be involved in the occurrence and development of PH, which may be related to the Smad2/3 signalling pathway. In vitro experiment: Human pulmonary artery smooth muscle cells were pretreated with the Gal-3 inhibitor (MCP) for 24 h, then TGF-β1 or Gal-3 was administered to the cells for 24 h. The results show that exogenous TGF-β1 and Gal-3 can activate the downstream Smad2/3 signalling pathway, and increase the proliferation and migration ability of HPASMC. However, the Gal-3 inhibitor (MCP) inhibited these effects. Further results display that TGF-β1 and Gal-3 could mutually regulate the protein and mRNA expression levels. In summary, the results of this study indicate that Gal-3 regulates the Smad2/3 signalling pathway through protein interaction with TGF-β1, in turn regulates the proliferation and migration of HPASMC, thereby regulating the occurrence and development of PH.

Keywords: Galectin-3; HPASMC; Migration; PH; Proliferation.

MeSH terms

  • Animals
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Humans
  • Male
  • Myocytes, Smooth Muscle / metabolism*
  • Pulmonary Artery / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Galectin 3
  • Lgals3 protein, rat
  • Transforming Growth Factor beta1