MiR-503 promotes wound healing of diabetic foot ulcer by targeting FBN1

MiR-503 promotes wound healing of diabetic foot ulcer by targeting FBN1
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MiR-503 通过靶向 FBN1 促进糖尿病足溃疡伤口愈合

DOI:
10.4103/1995-7645.228441
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发表时间:
2018-03
影响因子:
3.1
通讯作者:
Bi Chang Long
Bi Chang Long
中科院分区:
医学4区
文献类型:
--
作者:
Wang Ming Li;Chen Jing;Zhou Yue;Zhao Yu Jie;Sun De Rong;Wu Qiang;Bi Chang Long

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目的:探讨miR-503与糖尿病足溃疡创面愈合的关系。方法:采用基因芯片技术检测DFU组织与正常组织之间的miRNAs表达。采用定量逆转录聚合酶链式反应技术检测miR-503在DFU患者组织和血清中的表达。CCK-8比色法检测细胞增殖情况。用原位末端标记法检测miR-503作用后细胞的凋亡率。根据RNA22网站上的数据预测miR-503与fbillin1(FBN1)之间可能的相关性,并通过荧光素酶报告基因分析进行验证。结果:基因芯片分析显示,与正常组织相比,DFU组织中miR-503的表达水平显著降低。定量逆转录聚合酶链式反应证实,DFU患者组织和血清中miR-503的表达明显增加。CCK-8检测结果表明,miR-503模拟物的转染明显促进了细胞的增殖。然而,TUNEL检测表明miR-503模拟物通过抑制细胞的凋亡来提高成纤维细胞的存活率。此外,miR-503AMO在DFU组织成纤维细胞中的作用与miR-503模拟治疗完全相反。RNA22预测,MIR-503是对FBN1的补充。此外,siRNA-FBN1促进成纤维细胞的增殖,但抑制成纤维细胞的凋亡。结论:MIR-503通过直接靶向FBN1调控DFU患者成纤维细胞功能和创面愈合,为DFU的诊断和治疗提供了新的关键靶点。
Objective: To highlight the relationship between miR-503 and wound healing of diabetic foot ulcer (DFU). Methods: Microarray analysis was used to detect the dysregulated miRNAs between the DFU tissues and normal tissues. The expression of miR-503 in tissues and serum of patients with DFU was detected by qRT-PCR technique. Then, CCK-8 assay was applied to determine the cell proliferation. TUNEL assay was used for assessing the apoptosis of cells after treatment with miR-503. Possible correlation between miR-503 and fbillin1 (FBN1) was predicted according to data accessed on RNA22 website online, and was detected for confirmation by luciferase reporter assay. Results: Microarray analysis showed that miR- 503 was significantly decreased in the DFU tissues compared with normal tissues. While marked increase in the expression of miR-503 in tissues and serum of patients with DFU was confirmed by qRT-PCR technique. Then, CCK-8 assay indicated that transfection of miR- 503 mimic obviously accelerated the cell proliferation. However, TUNEL assays suggested that miR-503 mimic inhibited the apoptosis of cells to improve the survival of fibroblasts. Besides, miR-503 AMO played a role in fibroblasts of DFU tissues exactly countering to miR-503 mimic treatment. It was predicted that MiR-503 is a complementary to the FBN1 by RNA22. Besides, SiRNA-FBN1 promoted the proliferation, but brought down the apoptosis of fibroblasts. Conclusions: MiR-503 regulates the function of fibroblasts and wound healing of patients with DFU by targeting FBN1 directly which provids a novel and critical target for diagnosis and treatment of DFU.
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影响因子: 3.7
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DOI: 10.1016/j.bbrc.2017.09.099
发表时间: 2017-11-18
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