The role of thrombomodulin in diabetic wound healing

• Main Authors: Wei-KaiHuang, 黃韋愷
• Other Authors: Guey-Yueh Shi
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/93343817201619059956

碩士 === 國立成功大學 === 生物化學暨分子生物學研究所 === 100 === Diabetes mellitus (DM) is characterized as impaired glucose homeostasis. Persistently elevated blood glucose levels in patients with DM lead to complications, including inflammation, endothelial dysfunction, and poor wound healing. Keratinocyte migration and proliferation are required for re-epithelialization of cutaneous wounds and are important to restore barrier function of skin. Thrombomodulin (TM), an anticoagulant glycoprotein, is expressed by endothelial cells and epidermal keratinocytes. However, the expression and function of TM in epithelium remain unclear. In this study, higher expression of TM in the hyperproliferative epithelium (HE) at day 3 and day 5 after full-thickness excisional wound in mice was found, while the expression of TM was postponed at the wound margin in streptozotocin (STZ)-induced diabetic mice. The cell number of proliferating keratinocytes within the HE of control mice was higher than that of STZ-induced mice. Moreover, the effects of high glucose concentration on the expression of TM in keratinocytes and on keratinocyte proliferation and migration in vitro were investigated. High glucose treatment significantly decreased TM expression and inhibited keratinocyte proliferation and migration. In addition, transgenic mice that lack lectin-like domain of TM (TMLeD/LeD mice) exhibited delayed wound healing with higher infiltration of neutrophils and lower infiltration of macrophages when compared with TMWt/LeD mice. Taken together, these results suggest that TM may regulate keratinocyte proliferation and migration as well as inflammation, by which TM may control cutaneous wound healing.