Xu Dan, Guo Yu-Bing, Zhang Min, Sun Ye-Qing
Institute of Environmental Systems Biology, Dalian Maritime University, Dalian 116026, China.
Institute of Environmental Systems Biology, Dalian Maritime University, Dalian 116026, China; Department of Molecular Physiology and Medical Bioregulation, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, 755-8505, Japan.
Chin J Traumatol. 2018 Aug;21(4):229-237. doi: 10.1016/j.cjtee.2018.04.004. Epub 2018 Jun 28.
Microgravity is known to cause endothelium dysfunction in astronauts returning from spaceflight. We aimed to reveal the regulatory mechanism in alterations of human endothelial cells after simulated microgravity (SMG).
We utilized the rotary cell culture system (RCCS-1) to explore the subsequent effects of SMG on human umbilical vein endothelial cells (HUVECs).
SMG-treated HUVECs appeared obvious growth inhibition after return to normal gravity, which might be attributed to a set of responses including alteration of cytoskeleton, decreased cell adhesion capacity and increased apoptosis. Expression levels of mTOR and its downstream Apaf-1 were increased during subsequent culturing after SMG. miR-22 was up-regulated and its target genes SRF and LAMC1 were down-regulated at mRNA levels. LAMC1 siRNAs reduced cell adhesion rate and inhibited stress fiber formation while SRF siRNAs caused apoptosis.
SMG has the subsequent biological effects on HUVECs, resulting in growth inhibition through mTOR signaling and miR-22-mediated mechanism.
已知微重力会导致从太空飞行返回的宇航员出现内皮功能障碍。我们旨在揭示模拟微重力(SMG)后人内皮细胞改变的调控机制。
我们利用旋转细胞培养系统(RCCS-1)来探究SMG对人脐静脉内皮细胞(HUVECs)的后续影响。
经SMG处理的HUVECs在恢复正常重力后出现明显的生长抑制,这可能归因于一系列反应,包括细胞骨架改变、细胞黏附能力下降和细胞凋亡增加。在SMG后的后续培养过程中,mTOR及其下游的Apaf-1表达水平升高。miR-22上调,其靶基因SRF和LAMC1在mRNA水平下调。LAMC1小干扰RNA降低细胞黏附率并抑制应力纤维形成,而SRF小干扰RNA导致细胞凋亡。
SMG对HUVECs有后续生物学效应,通过mTOR信号传导和miR-22介导的机制导致生长抑制。