Department of Cardiovascular Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, China.
Department of Cardiovascular Medicine, The First Hospital of Xi'an, China.
Arch Biochem Biophys. 2019 Nov 30;677:108154. doi: 10.1016/j.abb.2019.108154. Epub 2019 Oct 28.
The proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the development and progression of diabetes-related vascular complications. Recently, microRNAs (miRNAs) have been suggested to be involved in the pathogenesis of vascular diseases. This study was designed to investigate the influences of tanshinone IIA, an active compound extracted from Chinese herb Salvia miltiorrhiza, on the proliferation and migration of human aortic VSMCs (HASMCs). cultured in a high glucose medium and the underlying mechanisms related miRNAs. Using a miRNA microarray method, we profiled the miRNA expression signature in human aortic VSMCs (HASMCs) exposed to normal glucose, high glucose with and without Tanshinone IIA. Cell proliferation was measured with 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Cell migration was evaluated using transwell migration assay and wound scratch assay. Western blot was used to examine the expression of tropomyosin 1 (TPM1) and miRNA level was quantified by real-time PCR. The results showed that several miRNAs that were highly expressed in the high glucose group were significantly decreased in the high glucose with Tanshinone IIA group compared with the normal glucose group (P < 0.05). Among these miRNAs, miR-21-5p was significantly upregulated in the high glucose group and downregulated after Tanshinone IIA treatment (P < 0.05). The depletion of miR-21-5p in HASMCs resulted in decreased cell proliferation and migration (P < 0.05). Moreover, we found that Tanshinone IIA inhibited proliferation and migration partly through miR-21-5p-mediated TPM1 downregulation (P < 0.05). In conclusion, the present study demonstrates that Tanshinone IIA is able to protect HASMCs from high glucose-induced proliferation and migration through regulating expression of miRNAs.
血管平滑肌细胞（VSMCs）的增殖和迁移在糖尿病相关血管并发症的发展和进展中起着重要作用。最近，microRNAs（miRNAs）被认为参与了血管疾病的发病机制。本研究旨在探讨丹参酮 IIA（一种从中药丹参中提取的活性化合物）对高糖培养的人主动脉血管平滑肌细胞（HASMCs）增殖和迁移的影响及其与相关 miRNAs 的潜在机制。我们使用 miRNA 微阵列方法对暴露于正常葡萄糖、高葡萄糖和丹参酮 IIA的人主动脉血管平滑肌细胞（HASMCs）的 miRNA 表达谱进行了分析。使用 5-溴-2'-脱氧尿苷（BrdU）掺入测定法测量细胞增殖。使用 Transwell 迁移测定法和划痕实验评估细胞迁移。使用 Western blot 检测原肌球蛋白 1（TPM1）的表达，并用实时 PCR 定量 miRNA 水平。结果表明，与正常葡萄糖组相比，高葡萄糖组中高表达的几种 miRNA 在高葡萄糖加丹参酮 IIA 组中显著降低（P<0.05）。在这些 miRNA 中，miR-21-5p 在高葡萄糖组中显著上调，在丹参酮 IIA 处理后下调（P<0.05）。在 HASMCs 中耗尽 miR-21-5p 可导致细胞增殖和迁移减少（P<0.05）。此外，我们发现丹参酮 IIA 通过 miR-21-5p 介导的 TPM1 下调部分抑制增殖和迁移（P<0.05）。总之，本研究表明丹参酮 IIA 能够通过调节 miRNAs 的表达来保护 HASMCs 免受高葡萄糖诱导的增殖和迁移。
