Variations in expressions of periostin and related factors in early stage of wound healing and scar remodeling in rats

Abstract

To investigate the expressions of periostin (PN), angiopoietin-1 (Ang-1), vascular epithelial growth factor (VEGF) and fetal liver kinase-1 (Flk-1) during the processes of scar formation and modulation in rat cutaneous wounds and probe into their roles in wound healing and scaring. Eighty-two male Sprague-Dawley (SD) rats were randomly divided into 10 groups with 8-9 rats in each group. Two 2 cm×2 cm full-thickness excisional wounds in the back were created in each rat. The wound surface was observed, and the healing area was measured. The pathological change was observed after hematoxylin and eosin (HE) staining. The expressions of PN, Ang-1, VEGF and Flk-1 in wound surface scar at 4-8 weeks were determined with immunohistochemistry. The expressions of PN, Ang-1 and VEGF were determined by Western blotting. The normal skin was served as control. HE staining showed that the wound surface tissue had healed with epithelization at 4-8 weeks. Immunohistochemistry results showed that there was no significant difference in Flk-1 expression between wound surface tissue and normal skin. The PN expression (A value/μm(2)) in wound surface tissue was significantly lower than that in normal skin at 5 weeks (2.43±0.44 vs. 4.24±0.50, P<0.05), and the expression of Ang-1 and VEGF (A value/μm(2)) at 4, 5, 6, 8 weeks was significantly lower than that in normal skin (Ang-1: 3.51±0.93, 3.10±0.57, 2.77±0.59, 2.77±1.26 vs. 4.89±0.48; VEGF: 1.76±0.68, 1.75±0.49, 1.99±0.42, 1.94±0.86 vs. 4.86±1.63, all P<0.05). In wound surface scar, PN and Flk-1 positive signal was found in cell, and the Ang-1 and VEGF positive signal in extracellular matrix. Western blotting data demonstrated that the expressions of PN, Ang-1 and VEGF peaked at the 10th day after excision with increases to 7.90-22.56 folds compared with normal skin (PN: 2.45±1.51 vs. 0.31±0.19, Ang-1: 18.43±15.20 vs. 1.53±1.42, VEGF: 6.09±4.66 vs. 0.27±0.13, P<0.05 or P<0.01), and then followed with a decrease. PN, Ang-1, VEGF and Flk-1 are transiently overexpressed in early stage of full-thickness cutaneous wound healing in rats. Their expressions vary in wounds and scars. They participate in the healing of full-thickness cutaneous wounds together and may be essential for the proliferation stage during wound healing.