Effects of glucose on human cultured keratinocyte migration and proliferation: an in vitro study of re-epithelialization in diabetic ulcer
| Autor: | I-Hsin Liu, 劉依欣 |
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| Rok vydání: | 2007 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 95 Diabetes mellitus (DM) is characterized by impaired insulin signaling, elevated plasma glucose, and a predisposition toward chronic complications involving several tissues. Among the chronic complication of DM, the dermatological complications are among the least thoroughly studied. Impaired wound healing is one of the major dermatological complications in diabetic patients. Normal wound healing can be divided into four phases: (1) hemostasis and inflammation phase; (2) re-epithelialization phase; (3) contraction and synthetic phase; (4) remodeling phase. In the re-epithelialization process during cutaneous wound healing, the migration and proliferation of keratinocytes (KCs) are crucial steps. Although numerous studies discussing the poor wound healing process in diabetics have been reported, the effects of glucose on KC migration and proliferation are scarcely studied. Our current studies aim to explore the effects of high glucose on cultured human KC migration and proliferation. Our results showed that the proliferation of KCs was significantly decreased by high glucose treatment. In addition, using in vitro wound scratch assay and Transwell migration assay, we demonstrated that the motility of KCs was significantly reduced under hyperglycemic condition. According to the aforementioned phenomena, we further investigated the possible molecular mechanisms involved. The results of RT-PCR revealed that high glucose treatment downregulated the expressions of MMP-1, MMP-2 and MMP-9 in KCs. Furthermore, the expression of TIMP-1 was increased after high glucose treatment. Focal adhesion kinase (p125FAK) plays a pivotal role in cell migration. In our study, expressions of p125FAK and phosphorylated p125FAK (pp125FAK) in KCs were decreased under hyperglycemic condition. In this study, we also demonstrated that high glucose inhibited the expression of integrin α2β1、α3β1 on KCs. In conclusion, our results indicated that the decrease in the migration and proliferation of KCs after high glucose treatment might be related to the inhibition of re-epithelialization during wound healing. Our results may provide in vitro evidences for poor wound healing in diabetic patients. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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