The Phytochemical Shikonin Stimulates Epithelial-Mesenchymal Transition (EMT) in Skin Wound Healing.
The Phytochemical Shikonin Stimulates Epithelial-Mesenchymal Transition (EMT) in Skin Wound Healing.
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DOI：
10.1155/2013/262796
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Yang NS
中科院分区：
文献类型：
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作者：
Yin SY;Peng AP;Huang LT;Wang YT;Lan CW;Yang NS
虽然紫草素的各种药理活性已被记录，但在基因组水平上理解这些不同生物活性的分级调节是未经证实的。在这项研究中，通过转录组和microRNA阵列分析之间的交叉检查，我们预测，紫草素在体内局部治疗影响上皮间质转化（EMT）和相关microRNA的表达，包括200 a，200 b，200 c，141，205，和429 microRNA，在小鼠皮肤组织中。原位免疫组化分析进一步表明，特定的EMT调节分子增强在紫草素处理的表皮组织。RT-PCR分析随后证实，紫草素处理下调microRNA-205和200家族microRNA的其他成员的表达。此外，在EMT调节中的200个家族microRNA中的两个RNA靶点Sip 1（Zeb 2）和Tcf 8（Zeb 1）的表达通过紫草素处理一致地上调。增强这些EMT活动也检测到紫草素治疗的伤口，修复速度比对照组。这些结果表明，紫草素的局部治疗可以赋予EMT一个强大的刺激作用，并抑制相关的microRNA在皮肤伤口愈合的表达。总的来说，这些细胞和分子数据提供了进一步的证据，支持我们以前的研究结果，在伤口愈合和免疫调节紫草素的具体药理作用。
Although various pharmacological activities of the shikonins have been documented, understanding the hierarchical regulation of these diverse bioactivities at the genome level is unsubstantiated. In this study, through cross examination between transcriptome and microRNA array analyses, we predicted that topical treatment of shikonin in vivo affects epithelial-mesenchymal transition (EMT) and the expression of related microRNAs, including 200a, 200b, 200c, 141, 205, and 429 microRNAs, in mouse skin tissues. In situ immunohistological analyses further demonstrated that specific EMT regulatory molecules are enhanced in shikonin-treated epidermal tissues. RT-PCR analyses subsequently confirmed that shikonin treatment downregulated expression of microRNA-205 and other members of the 200 family microRNAs. Further, expression of two RNA targets of the 200 family microRNAs in EMT regulation, Sip1 (Zeb2) and Tcf8 (Zeb1), was consistently upregulated by shikonin treatment. Enhancement of these EMT activities was also detected in shikonin-treated wounds, which repaired faster than controls. These results suggest that topical treatment with shikonin can confer a potent stimulatory effect on EMT and suppress the expression of the associated microRNAs in skin wound healing. Collectively, these cellular and molecular data provide further evidence in support of our previous findings on the specific pharmacological effects of shikonin in wound healing and immune modulation.