Endogenous microRNAs in human microvascular endothelial cells regulate mRNAs encoded by hypertension-related genes.
Endogenous microRNAs in human microvascular endothelial cells regulate mRNAs encoded by hypertension-related genes.
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DOI：
10.1161/hypertensionaha.115.05645
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Liang M
中科院分区：
文献类型：
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作者：
Kriegel AJ;Baker MA;Liu Y;Liu P;Cowley AW Jr;Liang M
本研究的目的是系统地鉴定内皮细胞中调节高血压相关基因编码的mRNA的内源性microRNA。在培养的人微血管内皮细胞中进行小RNA深度测序。在鉴定的50种最丰富的microRNA中，有30种预测了由已知参与高血压或血压调节的基因编码的靶mRNA。用抗miR寡核苷酸转染细胞以抑制30种microRNA中的每一种，并检查预测靶标的mRNA丰度。在检测的95个microRNA-靶对中，靶mRNA在35对中显著上调，在8对中矛盾地下调。结果表明，内源性miR-181 a-5 p显著抑制ADM编码的mRNA丰度，miR-27家族显著抑制ATP 2B 1编码的mRNA丰度，miR-125 a-5 p显著抑制FURIN编码的mRNA丰度，let-7家族显著抑制FGF 5编码的mRNA丰度，miR-27 a-3 p显著抑制GOSR 2编码的mRNA丰度，miR-21- 5 p显著抑制JAG 1编码的mRNA丰度，miR-30 a-5 p、miR-98、miR-181 a-5 p和miR-125家族显著抑制SH 2B 3编码的mRNA丰度，miR-92家族的TBX 3、miR-22- 3 p的ADRA 1B、miR-30 a-5 p和miR-30 e-5 p的ADRA 2A、miR-30 e-5 p的ADRA 2B、let-7家族和miR-98的ADRB 1、miR-92家族的EDNRB和miR-92家族、miR-100- 5 p和miR-99 b-5 p的NOX 4（n=3-9，P<0.05相对于乱序抗miR）。用抗miR-21治疗降低了喂食4%NaCl饮食的小鼠的血压。抑制靶向NOX 4 mRNA的microRNA增加了内皮细胞的H2 O2释放。研究结果表明，广泛的，紧张性控制的mRNAs编码的基因相关的血压调节内皮microRNAs，并提供了一个新的和独特的信息基础，研究microRNAs在高血压中的作用。
The goal of the present study was to systematically identify endogenous microRNAs in endothelial cells that regulate mRNAs encoded by genes relevant to hypertension. Small RNA deep sequencing was performed in cultured human microvascular endothelial cells. Of the 50 most abundant microRNAs identified, 30 had predicted target mRNAs encoded by genes with known involvement in hypertension or blood pressure regulation. The cells were transfected with anti-miR oligonucleotides to inhibit each of the 30 microRNAs and the mRNA abundance of predicted targets was examined. Of 95 microRNA-target pairs examined, the target mRNAs were significantly up-regulated in 35 pairs and paradoxically down-regulated in 8 pairs. The result indicated significant suppression of the abundance of mRNA encoded by ADM by endogenous miR-181a-5p, ATP2B1 by the miR-27 family, FURIN by miR-125a-5p, FGF5 by the let-7 family, GOSR2 by miR-27a-3p, JAG1 by miR-21-5p, SH2B3 by miR-30a-5p, miR-98, miR-181a-5p, and the miR-125 family, TBX3 by the miR-92 family, ADRA1B by miR-22-3p, ADRA2A by miR-30a-5p and miR-30e-5p, ADRA2B by miR-30e-5p, ADRB1 by the let-7 family and miR-98, EDNRB by the miR-92 family, and NOX4 by the miR-92 family, miR-100-5p, and miR-99b-5p (n=3–9, P<0.05 vs. scrambled anti-miR). Treatment with anti-miR-21 decreased blood pressure in mice fed a 4% NaCl diet. Inhibition of the microRNAs targeting NOX4 mRNA increased H2O2 release from endothelial cells. The findings indicate widespread, tonic control of mRNAs encoded by genes relevant to blood pressure regulation by endothelial microRNAs and provide a novel and uniquely informative basis for studying the role of microRNAs in hypertension.