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- Title
MicroRNA-129 and -335 Promote Diabetic Wound Healing by Inhibiting Sp1-Mediated MMP-9 Expression.
- Authors
Wei Wang; Chuan Yang; Xiao yi Wang; Li yan Zhou; Guo juan Lao; Dan Liu; Chuan Wang; Meng die Hu; Ting ting Zeng; Li Yan; Meng Ren; Wang, Wei; Yang, Chuan; Wang, Xiao Yi; Zhou, Li Yan; Lao, Guo Juan; Liu, Dan; Wang, Chuan; Hu, Meng Die; Zeng, Ting Ting
- Abstract
Diabetic wounds are recalcitrant to healing. However, the mechanism causing this dysfunction is not fully understood. High expression of matrix metalloproteinase-9 (MMP-9) is indicative of poor wound healing. In this study, we show that specificity protein-1 (Sp1), a regulator of MMP-9, binds directly to its promoter and enhances its expression. Additionally, we demonstrated that Sp1 is the direct target of two microRNAs (miRNAs), miR-129 and -335, which are significantly downregulated in diabetic skin tissues. In vitro experiments confirmed that miR-129 or -335 overexpression inhibits MMP-9 promoter activity and protein expression by targeting Sp1, whereas the inhibition of these miRNAs has the opposite effect. The beneficial role of miR-129 or miR-335 in diabetic wound healing was confirmed by the topical administration of miRNA agomirs in diabetic animals. This treatment downregulated Sp1-mediated MMP-9 expression, increased keratinocyte migration, and recovered skin thickness and collagen content. The combined treatment with miR-129 and miR-335 induced a synergistic effect on Sp1 repression and MMP-9 downregulation both in vitro and in vivo. This study demonstrates the regulatory mechanism of Sp1-mediated MMP-9 expression in diabetic wound healing and highlights the potential therapeutic benefits of miR-129 and -335 in delayed wound healing in diabetes.
- Subjects
PEOPLE with diabetes; MICRORNA genetics; WOUND healing; GENE expression; METALLOPROTEINASES
- Publication
Diabetes, 2018, Vol 67, Issue 8, p1627
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db17-1238