Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression
| Autor: | Tsung Lin Cheng, Kuan Chieh Wang, Guey Yueh Shi, Hua Lin Wu, Chia Fong Cho, Chao Han Lai, Bi Ing Chang, Yun Yan Hsu, Po Ku Chen, Chao Kai Hsu, Wei Ling Lin, Shi Kai Liu, Yu Ting Wu |
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| Rok vydání: | 2014 |
| Předmět: |
Keratinocytes
Thrombomodulin Dermatology Biochemistry Streptozocin Diabetes Mellitus Experimental Diabetes Complications Mice Downregulation and upregulation Cell Line Tumor Animals Humans Receptor Molecular Biology Skin Regulation of gene expression Wound Healing Chemistry Tumor Necrosis Factor-alpha Cell Biology Recombinant Proteins Mice Inbred C57BL Toll-Like Receptor 4 Glucose Gene Expression Regulation Cell culture Immunology Cancer research TLR4 Tumor necrosis factor alpha Wound healing Gene Deletion |
| Zdroj: | The Journal of investigative dermatology. 135(6) |
| ISSN: | 1523-1747 |
| Popis: | Keratinocyte-expressed thrombomodulin (TM) and the released soluble TM (sTM) have been demonstrated to promote wound healing. However, the effects of high glucose on TM expression in keratinocytes and the role of TM in diabetic ulcer remain unclear. In this study, we demonstrated that expressions of TM and Toll-like receptor 4 (TLR4) were both downregulated in high-glucose cultured human keratinocytes and in skin keratinocytes of diabetic patients. In addition, the wound-triggered upregulation of TM and sTM production was abolished in both high-glucose cultured human keratinocytes and streptozotocin-induced diabetic mouse skin. Furthermore, supplementation of recombinant sTM could increase TLR4 expression and promote cutaneous wound healing in both high-glucose cultured human keratinocytes and diabetic mice. However, in Tlr4-deleted mice, which exhibited delayed wound healing, the therapeutic benefit of recombinant sTM was abrogated. Moreover, our results showed that tumor necrosis factor-α (TNF-α) expression in keratinocytes was dose-dependently upregulated by glucose, and TNF-α treatment downregulated the expression of TM and TLR4. Taken together, high-glucose environment reduces the expression of TM and TLR4 in keratinocytes possibly through the action of TNF-α, and recombinant sTM can increase the TLR4 expression and promote wound healing under diabetic condition. |
| Databáze: | OpenAIRE |
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