Effect of annexin A2 on hepatopulmonary syndrome rat serum-induced proliferation of pulmonary arterial smooth muscle cells

Respir Physiol Neurobiol. 2013 Jan 15;185(2):332-8. doi: 10.1016/j.resp.2012.09.009. Epub 2012 Oct 8.

Abstract

Hepatopulmonary syndrome (HPS) is characterizes by an arterial oxygenation defect induced by intrapulmonary vasodilation that increase morbidity and mortality. However, the underlying mechanisms on HPS-associated pulmonary vascular remodeling remains undefined. In this study, we found that HPS rat serum, drawn from common bile duct ligation (CBDL) rats, mediated the overexpression of ANXA2 and the proliferation of PASMCs. And small interfering RNA (siRNA) that target rat ANXA2 led to significant downregulation of ANXA2, which resulted in the decreased proliferation of PASMCs. Subsequently, we further examined the role of ANXA2 siRNA in the regulation of pro-proliferative signaling such as that mediated by ERK1/2 and NF-κB, and found the attenuation of HPS-associated activation of the signaling pathway. Thus, the fact highlighted the crucial role of ANXA2 in HPS-associated PASMC proliferation, and suggested a potential therapeutic effect on HPS-associated pulmonary vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A2 / genetics
  • Annexin A2 / metabolism*
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Hepatopulmonary Syndrome / blood
  • Hepatopulmonary Syndrome / pathology*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Pulmonary Artery / cytology*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Serum* / chemistry
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Statistics, Nonparametric
  • Tetrazolium Salts
  • Thiazoles
  • Thymidine / metabolism
  • Transfection

Substances

  • Annexin A2
  • RNA, Messenger
  • RNA, Small Interfering
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • Thymidine