Deletion of Calponin 2 Reduces the Formation of Postoperative Peritoneal Adhesions

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
• myofibroblast
• inflammation
• peritoneal adhesions

Acknowledgements

TBH was a recipient of Women’s Reproductive Health Research fellowship program from National Institute of Child Health and Human Development (HD001254 to Dr. Chaur-Dong. Hsu).

Disclosure statement

The authors declare that they have no conflict of interest.

Author’s contributions

JPJ conceived and designed research; TBH and HZF conducted experiments and analyzed data; TBH prepared figures and drafted manuscript; TBH and JPJ revised and approval final version of manuscript.

Additional information

Funding

This study was supported in part by a grant from the National Heart, Lung and Blood Institute (HL138007 to JPJ).