| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 105 === Diabetes mellitus, a chronic disease, is associated with the defect of insulin secretion and function. It has been reported that about 15% of diabetic patients will have diabetic mellitus foot (DMF) , and 85% of these patients will need amputation. We may develop a more effective treatment, if we can learn the reason of DMF. In order to understand the mechanism of DMF, we also use acute wounds as comparison.
It has been reported that matriptase, a type II transmembrane serine protease, may regulate the proliferation and early differentiation of human keratinocytes; and prostasin, a glycosylphosphatidylinisotol (GPI) -anchored serine protease, may be involved in the late differentiation and barrier function of skin. Hepatocyte growth factor activator inhibitors (HAIs) have two Kunitz-type domains which enable HAIs to inhibit and regulate serine proteases. Two members of HAIs are HAI-1 and HAI-2. Recent studies have shown that matriptase can activate pro-HGF to become HGF. HGF can binds with it’s receptor c-Met to activate the downstream process which are critical for healing, such as the proliferation process. So we want to analyze the different expressions of matriptase, prostasin, HAI-1, HAI-2 and the related proteins between diabetic ulcer and acute trauma. As the results, we discovered the expression area of total matriptase will be narrow after trauma and may restore after 3 days or longer and the ratio of the activated matriptase will be increased after 3 days. Total and activated prostasin will be expressed wider after trauma just like the expression in DM ulcers. As we found previously, the expression of HAI-1 is decreased in DM ulcers, but the expression of HAI-1 is not decreased in the adjacent epidermis of acute wounds and normal skins. HAI-2 is expressed weakly in normal skins, but the expression of HAI-2 in the adjacent epidermis of acute wounds and few DM foot wounds become stronger and wider. No matter in normal skins, DM foot or acute trauma, c-Met is expressed in basel layer. K15, as the stem cell marker of skin, is expressed in normal skins, but rarely expressed in the adjacent epidermis of DM foot. In acute trauma, the expression ratio of K15 was decreased obviously after 3 days of trauma, but was recovered after 7 days of trauma. Collect these results, we suggest that the expression of activated matriptase and stronger HAI-2 may accelerate the speed of wound healing.
As we have discovered HAI-2 was expressed strongly from basal layer to lower spinous layer in the cytosol after wounding, meanwhile prostasin is expressed in the cytosl of upper spinous layer, and the site which HAI-2 is not expressed near the place where prostasin is expressed on the cell membrane. As the results, we speculate HAI-2 may play a role as a prostasin inhibitor in a specific healing stage.
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