Annexin A2-modulated proliferation of pulmonary arterial smooth muscle cells depends on caveolae and caveolin-1 in hepatopulmonary syndrome

Exp Cell Res. 2017 Oct 1;359(1):266-274. doi: 10.1016/j.yexcr.2017.07.020. Epub 2017 Jul 17.


We have established that annexin A2 (ANXA2) is an important factor in the experimental hepatopulmonary syndrome (HPS) serum-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs). However, the detailed mechanism remains unclear. ANXA2 translocated to the caveolin-enriched microdomains (caveolae) in PASMCs upon HPS serum stimulation. The disruption of caveolae by Methyl-β-cyclodextrin (MβCD) alleviated the caveolae recruitment of ANXA2 and the ANXA2-mediated activation of ERK1/2 and NF-κB, so that ANXA2-modulated PASMC proliferation was suppressed. The over-expression of Cav-1 resulted in the relocation of ANXA2 from caveolae and negatively regulated ERK1/2 and NF-κB activation, which inhibited the ANXA2-modulated PASMC proliferative behavior. These data indicate that caveolae function as a signaling platform for ANXA2-induced proliferative behavior and Cav-1 participates upstream of ANXA2 in the activation of ERK1/2 and NF-κB.

Keywords: Annexin A2; Caveolae; Caveolin-1; Proliferation; Pulmonary arterial smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A2 / metabolism*
  • Caveolae / metabolism*
  • Caveolin 1 / chemistry
  • Caveolin 1 / metabolism*
  • Cell Proliferation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hepatopulmonary Syndrome / blood
  • Hepatopulmonary Syndrome / metabolism*
  • Hepatopulmonary Syndrome / pathology*
  • Male
  • Myocytes, Smooth Muscle / pathology*
  • NF-kappa B / metabolism
  • Protein Domains
  • Pulmonary Artery / pathology*
  • Rats, Sprague-Dawley
  • beta-Cyclodextrins


  • Annexin A2
  • Caveolin 1
  • NF-kappa B
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • Extracellular Signal-Regulated MAP Kinases