miR-203 Acts as an Inhibitor for Epithelial-Mesenchymal Transition Process in Diabetic Foot Ulcers via Targeting Interleukin-8
| Autor: | Yang Sun, Meili Xu, Xiang Xiong, Fanglin Zeng, Liqin Yuan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Glycation End Products
Advanced Keratinocytes Epithelial-Mesenchymal Transition Receptor for Advanced Glycation End Products Immunology Gene Expression Cell Line 03 medical and health sciences 0302 clinical medicine Endocrinology Downregulation and upregulation Cell Movement medicine Animals Humans Vimentin Interleukin 8 Epithelial–mesenchymal transition PI3K/AKT/mTOR pathway Wound Healing Endocrine and Autonomic Systems business.industry Interleukin-8 Cell migration Cadherins Diabetic Foot Rats 030227 psychiatry MicroRNAs medicine.anatomical_structure Neurology Gene Knockdown Techniques Cancer research Snail Family Transcription Factors Wound healing Keratinocyte business miR-203 030217 neurology & neurosurgery |
| Zdroj: | Neuroimmunomodulation. 26:239-249 |
| ISSN: | 1423-0216 1021-7401 |
| DOI: | 10.1159/000503087 |
| Popis: | Objectives: As a complication of diabetes mellitus (DM), one of the leading causes for death and disability for DM patients is diabetic foot ulcers (DFUs). Epithelial to mesenchymal transition (EMT) plays a critical role in wound healing of DFUs. miR-203 is specifically enriched in keratinocytes and has been shown to target interleukin 8 (IL-8), which acts as an activator for the EMT process. In this study, we explored the interaction between miR-203 and IL-8 in DFU rat models and human keratinocyte cells, underlying the mechanism of miR-203’s function in DFUs progression. Methods: DFU rat models were used to test gene expression in DFU progression. Diabetic keratinocyte cell lines were used to validate in vitro. Wound healing and Transwell assays were applied to evaluate cell migration and invasion abilities. The EMT process was estimated by testing expression of E-cadherin, Vimentin and Slug. The interaction between miR-203 and IL-8 was determined by Luciferase assay. Results: Our results demonstrated that the wound-healing process had been slowed in DFUs, and the advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGEs) in wound tissue were of a higher expression than those in normal rat. miR-203 was increased in skin tissues from DFU rat models, while IL-8 was decreased. Through knock-down of miR-203 in AGE-treated keratinocyte cells, it had been shown that the downregulation of miR-203 could promote cell proliferation and migration, and facilitate the EMT process. Meanwhile, Luciferase assay proved that miR-203 could directly target and inhibit IL-8. The repression of IL-8 could rescue the outcomes brought about by miR-203 inhibition. Conclusions: The upregulation of miR-203 in DFU tissues impaired wound healing by the repress EMT process. Specific knock-down of miR-203 could promote wound healing through the reactivation of its target gene IL-8 and the downstream IL-8/AKT pathway. |
| Databáze: | OpenAIRE |
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