Expression of TGF-beta Induced Protein, betaig-h3, in Chronic Wound and It's Effect on Wound Healing

ABSTRACT

betaig-h3 is highly induced in A549 cells(human lung adenocarcinoma) after growth arrest by transforming growth factor-beta1. Although some reports describe variable functions of betaig-h3, it's function is in part controversial. betaig-h3 is a TGF-beta inducible cell adhesion molecule and some authors contend that recombinant betaig-h3 supports attachment and spreading of dermal fibroblast. Thus, it is expected that betaig-h3 plays a good role in wound healing. In order to investigate the effect of betaig-h3 in wound healing, The expression of TGF-beta and betaig-h3 in normal skin tissues and chronic wounds were examined by immunohistochemistry stain. In addition, 5 types of recombinant betaig-h3 were made, and among them, betaig-h3 b and betaig-h3 e were used for the experiment. Sprague- Dawley white rats served as the experimental models. Four round full-thickness skin defects of 2cm diameter were made on the back of each rat. The experiment was divided into 4 groups according to the content of ointment; group A Topical application of ointment base only, group B Topical application of ointment containing fibronectin 100microgram/ml, group C Topical application of ointment containing betaig-h3 b 100 microgram/ml, group D Topical application of ointment containing betaig-h3 e 100microgram/ml. In immunohistochemical study on normal human skin, the expression of TGF-beta was located in the upper dermal part, stratum basale, stratum spinosum and stratum granulosum in epidermis. The expression of betaig-h3 in normal dermis was similar with that of TGF-beta, but increased staining was observed in only stratum basale of normal epidermis. In chronic wounds, TGF-beta and betaig-h3 were highly expressed beneath the bottom and margin of wound and there were some cells showing positive staining within the nucleus. In animal models applied ointment, the reduction of wound size was more marked in group B, C, D than in group A. More rapid reepithelialization, less fibroplasia, less infiltration of inflammatory cells, more capillary formation in early period and more rapid collagen formation were seen in betaig-h3 treated wounds. In conclusion, betaig-h3 plays an important role in wound healing, and it is expected that recombinant betaig-h3 will become potent material for the treatment of chronic wound.