DFMG reverses proliferation and migration of vascular smooth muscle cells induced by co-culture with injured vascular endothelial cells via suppression of the TLR4-mediated signaling pathway.
DFMG reverses proliferation and migration of vascular smooth muscle cells induced by co-culture with injured vascular endothelial cells via suppression of the TLR4-mediated signaling pathway.
复制标题
DOI：
10.3892/mmr.2018.8635
复制
发表时间：
2018-04
影响因子：
3.4
通讯作者：
Fu X
中科院分区：
文献类型：
--
作者：
Cong L;Zhang Y;Huang H;Cao J;Fu X
7-二氟甲氧基-5，4 ′-二甲氧基染料木黄酮（DFMG）是以染料木黄酮为原料合成的一种新型化合物。已有研究表明DFMG可通过调节线粒体凋亡途径逆转血管内皮细胞凋亡。本研究旨在利用Transwell插入物建立的非接触共培养模型，探讨DFMG介导的血管平滑肌细胞（VSMC）保护作用的活性和分子机制。ELISA法检测IL-6和TNF-α的分泌。分别使用细胞计数试剂盒-8和伤口愈合测定来评估VSMC的增殖和迁移。采用逆转录-定量聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blotting）分别检测Toll样受体4（TLR 4）mRNA和蛋白水平。溶血磷脂酰胆碱（LPC）可显著增加血管内皮细胞分泌IL-6和TNF-α。LPC处理的VECs可明显促进VSMCs增殖和迁移，DFMG可抑制LPC处理的VECs增殖和迁移。转染TLR 4短发夹状RNA（shRNA）或TLR 4 cDNA分别抑制和促进VSMCs增殖和迁移。此外，转染TLR 4 shRNA的VECs抑制了与受损VECs共培养诱导的VSMCs的增殖和迁移，DFMG处理进一步增强了这种抑制作用。与此相反，转染TLR 4 cDNA的VECs促进VSMCs的增殖和迁移，这种作用被DFMG抑制。总而言之，本研究的结果表明，DFMG可以通过抑制TLR 4介导的信号通路来逆转与受损VEC共培养诱导的VSMC的增殖和迁移。
7-Difluoromethoxy-5,4′-dimethoxy-genistein (DFMG) is a novel chemical compound synthesized using genistein. Previous studies have indicated that DFMG can reverse the apoptosis of vascular endothelial cells (VECs) by regulating the mitochondrial apoptosis pathway. The present study aimed to investigate the activity and molecular mechanism underlying DFMG-mediated protection of vascular smooth muscle cell (VSMCs) using a non-contact co-culture model established by using Transwell insert. Secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA. Proliferation and migration of VSMCs were assessed using a Cell Counting kit-8 and wound healing assays, respectively. Toll-like receptor 4 (TLR4) mRNA and protein levels were detected by reverse transcription-quantitative polymerase chain reaction and western blotting analyses, respectively. In the present study, lysophosphatidylcholine (LPC) significantly increased the secretion of IL-6 and TNF-α in VECs. VECs treated with LPC markedly increased proliferation and migration of VSMCs, which were inhibited by DFMG. Transfection of either TLR4 short hairpin RNA (shRNA) or TLR4 cDNA in VECs inhibited and increased proliferation and migration of VSMCs, respectively. Furthermore, transfection of VECs with TLR4 shRNA suppressed the proliferation and migration of VSMCs induced by co-culture with injured VECs, which was further enhanced by treatment with DFMG. By contrast, transfection of VECs with TLR4 cDNA enhanced proliferation and migration of VSMCs and this effect was inhibited by treatment with DFMG. Taken together, the results of the present study demonstrated that DFMG can reverse proliferation and migration of VSMCs induced by co-culture with injured VECs via suppression of the TLR4-mediated signaling pathway.
登录
查看更多内容
影响因子：
2.4
作者：
Ma, Weiwei;Ding, Bingjie;Xiao, Rong
通讯作者：
Xiao, Rong
影响因子：
2.7
作者：
Fu, Xiao-Hua;Wang, Li;Cao, Jian-Guo
通讯作者：
Cao, Jian-Guo
影响因子：
2.8
作者：
Ding, Hong;Li, Dongye;Wang, Cheng
通讯作者：
Wang, Cheng
影响因子：
3.4
作者：
Wang XQ;Wan HQ;Wei XJ;Zhang Y;Qu P
通讯作者：
Qu P
影响因子：
4.3
作者：
Cibor, Dorota;Domagala-Rodacka, Renata;Owczarek, Danuta
通讯作者：
Owczarek, Danuta