Deletion of Calponin 2 Reduces the Formation of Postoperative Peritoneal Adhesions

J Invest Surg. 2022 Mar;35(3):517-524. doi: 10.1080/08941939.2021.1880672. Epub 2021 Feb 23.

Abstract

Aim of the study: Postoperative peritoneal adhesions are a common cause of morbidity after surgery, resulting in multiple complications. Macrophage-mediated inflammation and myofibroblast differentiation after tissue injury play central roles in the pathogenesis and progression of adhesion formation. Calponin 2 is an actin cytoskeleton regulatory protein in endothelial cells, macrophages and fibroblasts that are key players in the development of fibrosis. Deletion of calponin 2 has been shown to attenuate inflammatory arthritis, atherosclerosis and fibrocalcification of the aortic valves. The present study investigated the effect of calponin 2 deletion on attenuating the formation of peritoneal adhesions in a mouse model for potential use as a new therapeutic target.Materials and methods: Sterile surgical procedures under general anesthesia were used on paired wild type (WT) and calponin 2 knockout (KO) mice to generate mild injury on the cecal and abdominal wall peritonea. Three and seven days post-operation, the mice were compared postmortem for the formation of peritoneal adhesions. Tissues at the adhesion sites were examined with histology and immunofluorescent studies for macrophage and myofibroblast activations.Results: Quantitative scoring demonstrated that calponin 2 KO mice developed significantly less postoperative peritoneal adhesions than that in WT mice. Calponin 2 deletion resulted in less infiltration of F4/80+ macrophages at the adhesion sites with less myofibroblast differentiation and collagen deposition than WT controls.Conclusions: The data show that deletion of calponin 2 effectively reduces postoperative peritoneal adhesion, presenting a novel molecular target for clinical prevention.

Keywords: Calponin 2; inflammation; myofibroblast; peritoneal adhesions.

MeSH terms

  • Animals
  • Calmodulin-Binding Proteins / genetics*
  • Endothelial Cells*
  • Mice
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Peritoneal Diseases*
  • Postoperative Complications / genetics
  • Postoperative Complications / prevention & control
  • Tissue Adhesions / genetics
  • Tissue Adhesions / prevention & control

Substances

  • Calmodulin-Binding Proteins
  • Cnn2 protein, mouse
  • Microfilament Proteins