MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar.
MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar.
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DOI：
10.1371/journal.pone.0123054
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tredget EE
中科院分区：
文献类型：
--
作者：
Kwan P;Ding J;Tredget EE
增生性瘢痕是皮肤深度烧伤后常见的纤维增生性并发症，可导致功能受损和终身毁容。核心蛋白聚糖在许多组织中减少纤维化并诱导再生，并且在增生性瘢痕和正常深层真皮成纤维细胞中显著下调。据推测，这些成纤维细胞中的microRNA下调核心蛋白聚糖，阻断它们将增加核心蛋白聚糖，并可能预防肥厚性瘢痕形成。与正常皮肤相比，在增生性瘢痕中发现较低的核心蛋白聚糖水平，并且与浅表真皮相比，在深层真皮中发现较低的核心蛋白聚糖水平。核心蛋白聚糖3'非翻译区报告基因分析表明，microRNA减少了深层真皮成纤维细胞中的核心蛋白聚糖，microRNA筛选预测miR- 24、181 b、421、526 b或543为候选者。在发现深层真皮成纤维细胞中mir-181 b水平增加后，证明TGF-β1刺激降低miR-24但增加miR-181 b，并且肥厚性瘢痕和深层真皮含有增加水平的miR-181 b。通过用miR-181 b阻断miR-181 b，有可能增加真皮成纤维细胞中核心蛋白聚糖蛋白的表达。这表明miR-181 b参与了皮肤和伤口愈合中核心蛋白聚糖的差异表达。此外，阻断miR-181 b逆转了TGF-β1诱导的核心蛋白聚糖下调和增生性瘢痕成纤维细胞的肌成纤维细胞分化，这表明了增生性瘢痕的潜在治疗。
Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3’ un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β1 induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.
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影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
6.5
作者：
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3.4
作者：
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影响因子：
1.4
作者：
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通讯作者：
Tredget, Edward E.
影响因子：
64.5
作者：
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