Study on the Role of Tumor Endothelial Marker 1 in Wound Healing

Abstract

Tumor endothelial marker 1 (TEM1) is also known as endosialin It is composed of six domains a C-type lectin-like domain a sushi domain a domain with three epidermal growth factor-like (EGF) repeats a mucin-like domain a transmembrane domain and a cytoplasmic domain Previous studies demonstrated that Tem1 was expressed abundantly in the skin of mouse embryos but the expression was quickly down-regulated after birth However the functions of Tem1 in skin physiology still need to be further investigated In vitro study the scratched wound assay was used on skin fibroblasts to mimic wound healing in vivo The results revealed that Tem 1 mRNA levels in skin fibroblasts were significantly up-regulated by scratch injury The similar results were observed when skin fibroblasts were treated with transforming growth factor beta 1 (TGF-β1) through phosphorylating the MAP kinase ERK Furthermore cell adhesion migration and proliferation were strongly inhibited in Tem1 stable knockdown fibroblasts In addition we utilized the Tem1-lacZ knock-in reporter gene mice obtained from Dr Shu-Wha Lin National Taiwan University Taiwan to screen which cells express Tem1-lacZ encoding β-galactosidase activity in the process of wound healing The results of in vivo studies showed that β-galactosidase activity was initially detectable in dermis at day 5 and subsequently up-regulated at day 7 and day 9 after skin injury Results of immunostaining data showed that specific marker of myofibroblasts ?-smooth muscle actin were detected in β-galactosidase positive cells Moreover delayed wound closure was observed in Tem1-knockout mice than wild-type mice Taken together our results suggest that TEM-1 in dermal fibroblasts should play a role in the process of cutaneous wound healing

Date of Award	2014 Aug 6
Original language	English
Supervisor	Hua-Lin Wu (Supervisor)