145 Biological Effects of Calreticulin on Wound Repair

Abstract

Calreticulin (CRT) is a major classic Ca‐binding chaperone protein of the endoplasmic reticulum. Recently, CRT has been recognized to have widespread extracellular effects as well. In the current study we show that CRT increases both epithelial migration and granulation tissue formation in models of porcine and murine wound repair. Partial thickness wounds were created on the paravertebral area of pigs (n = 4) and 0.1% and 0.5% CRT, and PDGF (positive control) applied for 4 consecutive days. In wounds harvested at 5 days, CRT induced a 28 and 22% greater extent of reepithelialization than PDGF and Tris/Ca buffer control, respectively (% healed = 56/CRT; 40.5/PDGF; 44/control). In addition, CRT stimulated earlier granulation tissue formation in a dose‐dependent manner (cumulative dermal depth, microns: 1615/CRT; 1250/PDGF; 1325/control). A similar granulation tissue inducing effect of CRT was also observed in a steroid‐impaired pig model. As a diabetic model of wound repair, two 5 mm circular full‐thickness wounds were created on the dorsum of db/db mice; the wounds were splinted open with silicone rings and covered with occlusive dressing (n = 24). After 5 days of treatment with 0.1, 0.5, and 5% CRT, a dose‐dependent 8‐, 4.5‐, and 2‐fold increase in granulation tissue formation was observed (p < 0.05). However, there was no apparent effect on wound closure. Tissue sections showed a highly cellular dermis in the CRT treated wounds. In addition, CRT (50 pg/ml) stimulated wound closure in a scratch plate assay using fibroblasts by 45%, in 48 hrs, compared to 2% for the control. Therefore, CRT may be a novel agent for wound healing by acting as a chemoattractant for cells involved in wound remodeling and in epithelial migration.Suppported by Calretex, LLC. NJ, USA (LIG) and the Alumni Fund, Alumni Association Downstate College of Medicine (MJC).