Liu X C, Wu S H, Wang W Y, Hao Q, Guo Z D, Wang W Z
Department of Obstetrics & Gynecology, Shanxi Academy of Medical Sciences & Shanxi Da Yi Hospital, Shanxi Da Yi Hospital Affiliated to Shanxi Medical University, Taiyuan 030032, China.
Department of Obstetrics & Gynecology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Zhonghua Yi Xue Za Zhi. 2019 Feb 19;99(7):510-514. doi: 10.3760/cma.j.issn.0376-2491.2019.07.007.
Exosomes are considered to mediate intercellular communication by delivering biomolecules like mRNA, miRNA into recipient cells. The purpose of this study was to evaluate the effects of exosomes secreted by fibroblasts from women with stress urinary incontinence (SUI-EXO) on endothelial cells angiogenesis. Primary fibroblasts were acquired from periurethral vaginal wall tissues and exosomes were prepared by ultracentrifugation of fibroblasts cells conditioned medium. The expression levels of pro-angiogenic and anti-angiogenic genes were assessed using qRT-PCR analysis. Migration of endothelial cells was measured by transwell assay, and the effects of SUI-EXO on angiogenesis were evaluated by performing a tube formation assay in vitro. SUI-EXO was successfully isolated from fibroblasts cells conditional medium and transferred to endothelial cells efficiently. When the endothelial cells were treated with SUI-EXO, the expression levels of pro-angiogenic genes in fibroblasts were downregulated, and the expression levels of anti-angiogenic genes were upregulated significantly (0.01). Endothelial cells exhibited a decreased migratory capacity after treatment with SUI-EXO compared to exosomes from health women (64.6±8.7 vs 114.5±14.2,0.01), and tube formation of endothelial cells was also significantly inhibited in the SUI-EXO treated group as determined by the increase of the tube length (87.6±13.3 vs 168.5±28.3,0.01). This study suggests that SUI-EXO plays related roles in regulating endothelial cells angiogenesis and SUI-EXO maybe involve in the pathogenesis of SUI.
外泌体被认为可通过将mRNA、miRNA等生物分子传递到受体细胞中来介导细胞间通讯。本研究的目的是评估压力性尿失禁女性成纤维细胞分泌的外泌体(SUI-EXO)对内皮细胞血管生成的影响。从尿道周围阴道壁组织获取原代成纤维细胞,并通过对成纤维细胞条件培养基进行超速离心来制备外泌体。使用qRT-PCR分析评估促血管生成和抗血管生成基因的表达水平。通过Transwell实验测量内皮细胞的迁移,并通过体外进行管腔形成实验评估SUI-EXO对血管生成的影响。SUI-EXO成功地从成纤维细胞条件培养基中分离出来,并有效地转移到内皮细胞中。当用SUI-EXO处理内皮细胞时,成纤维细胞中促血管生成基因的表达水平下调,抗血管生成基因的表达水平显著上调(P<0.01)。与健康女性的外泌体相比,用SUI-EXO处理后内皮细胞的迁移能力降低(64.6±8.7对114.5±14.2,P<0.01),并且通过管腔长度的增加确定,在SUI-EXO处理组中内皮细胞的管腔形成也受到显著抑制(87.6±13.3对168.5±28.3,P<0.01)。本研究表明,SUI-EXO在调节内皮细胞血管生成中起相关作用,并且SUI-EXO可能参与压力性尿失禁的发病机制。