Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China.
Exp Cell Res. 2018 Apr 1;365(1):24-32. doi: 10.1016/j.yexcr.2018.02.009. Epub 2018 Feb 15.
BACKGROUND/AIM: Increasing evidence show microRNAs (miRNAs) are associated with hepatopulmonary syndrome (HPS). The aim of this study was to investigate the role of miR-144 in the angiogenesis of HPS, as well as to identify its underlying mechanism.
The expression levels of miR-144-3p were assessed in pulmonary micro-vascular endothelial cells (PMVECs), as well as in lung tissues from rats with HPS. We predicted the potential target of miR-144-3p. Tyrosine kinase 2(Tie2) was identified as a target gene of miR144-3p, which has an essential role in the angiogenesis of lung vessel. In addition, the effects of miR-144-3p regulated on Tie2 was examined. The upregulation and down-regulation of miR-144-3p can affect the proliferation of PMVECs.
We found that the levels of miR-144-3p were frequently downregulated in HPS tissues and cell lines, and overexpression of miR-144-3p dramatically inhibited PMVECs proliferation and cell cycle. We further verified the Tie2 as a novel and direct target of miR-144-3p in HPS.
miR-144-3p can negatively regulate PMVECs proliferation by Tie2 expression. In addition, overexpression of miR-144-3p may prove beneficial as a therapeutic strategy for HPS treatment.
背景/目的：越来越多的证据表明 microRNAs（miRNAs）与肝肺综合征（HPS）有关。本研究旨在探讨 miR-144 在 HPS 血管生成中的作用及其潜在机制。
检测 HPS 大鼠肺微血管内皮细胞（PMVECs）和肺组织中 miR-144-3p 的表达水平。我们预测了 miR-144-3p 的潜在靶基因。Tie2 被鉴定为 miR144-3p 的靶基因，在肺血管的血管生成中起着至关重要的作用。此外，还研究了 miR-144-3p 对 Tie2 的调节作用。miR-144-3p 的上调和下调可以影响 PMVECs 的增殖。
我们发现，miR-144-3p 的水平在 HPS 组织和细胞系中经常下调，miR-144-3p 的过表达显著抑制 PMVECs 的增殖和细胞周期。我们进一步验证了 Tie2 是 HPS 中 miR-144-3p 的一个新的直接靶基因。
miR-144-3p 可以通过 Tie2 表达负调控 PMVECs 的增殖。此外，miR-144-3p 的过表达可能对 HPS 的治疗具有有益作用。
