MicroRNA-21 对肺高压血管 平滑肌细胞增殖的影响

Role of MicroRNA-21 on proliferation of vascular smooth muscle cells in pulmonary hypertension

摘要:

目的 研究microRNA-21（miRNA-21）在Wnt/β-catenin 信号通路中抑制肺高压（PH）血 管平滑肌细胞增殖的可能机制。方法 复制外源性miRNA-21 干扰的野百合碱大鼠肺高压原代肺动脉平滑 肌细胞（PASMCs）模型，分别用Western blot 和实时荧光定量PCR 检测外源性miRNA-21 对Wnt 通路 中β-catenin、Cyclin D1 和拮抗剂DDK1 表达的影响。结果 外源性抑制miRNA-21 表达时，PASMCs 中 β-catenin、Cyclin D1 表达水平增高，拮抗剂DDK1 表达降低，拮抗作用减弱；而外源性上调miRNA-21 表达时，PASMCs 中β-catenin、Cyclin D1 表达水平降低，拮抗剂DDK1 表达增高，拮抗作用增强。结论 miRNA-21 的早期干预可通过调控Wnt 通路的拮抗剂DKK1 作用与Wnt/β-catenin 信号通路参与PH 肺血 管重构。

Abstract:

Objective To study the role of MicroRNA-21 on proliferation of pulmonary vascular smooth muscle cells in pulmonary hypertension and potential mechanisms. Methods Rat model of monocrotaline-induced pulmonary hypertension (PH) was established. Primary pulmonary artery smooth muscle cells were isolated and treated with various insults. Western blot and Real-time fluorescent quantitative PCR were performed for determination of expression of β-catenin, Cyclin D1 and antagonist of DDK1. Results The level of β-catenin and Cyclin D1 was increased while DDK1 was decreased significantly when exogenous MicroRNA-21 was inhibited. However, upregulation of exogenous MicroRNA-21 induced decreased levels of β-catenin and Cyclin D1 increased levels of antagonist of DDK1. Conclusions Early intervention of MicroRNA-21 participates in pulmonary remodeling in PH model through regulating Wnt/β-catenin signaling pathway.