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肺动脉高压是一种高发性慢性疾病,目前的研究显示其机制还不完全清楚,可能和基因、环境和膳食习惯等因素密切相关。最近的研究显示,微小RNA(miRNA)直接或间接参与肺动脉高压的形成。如miR-143/145表达增加并控制miR-143/145-转录因子(KLF4/KLF5)-平滑肌肌动蛋白(SMA)、钙调节蛋白(calponin)和平滑肌22α蛋白(SM22-α)信号通路,导致平滑肌细胞(SMC)分化同时抑制其增生;与miR-143/145相似,miR-21表达增加并通过miR-21-过氧化物酶体增殖物激活受体α(PPARα)-SMA、calponin、SM22-α-SMC信号通路导致SMC分化,同时抑制SMC增生;miR-204在miR-204-信号转导和转录激活因子3(STAT3)-激活T细胞核因子(NFAT)-BCL2信号通路中发挥作用,最终导致血管收缩和肺动脉平滑肌细胞(PASMC)增生;miR-206在miR-206-缺氧诱导因子1α(HIF-1α)-线粒体功能通路中导致线粒体的功能改变;miR-424/503控制miR-424/503-成纤维细胞生长因子(FGF)2/FGFR1-丝裂原活化蛋白激酶信号途径(MAPK)-KLF2-内皮型一氧化氮合酶(eNOS)信号通路,导致内皮细胞和SMC的增生。此外,由于缺氧导致miR-328水平的改变,进而影响L-型钙通道-αC蛋白的表达,从而导致肺动脉高压。miRNA由于其分子量小,易于合成和修饰,将会成为治疗肺动脉高压的有效药物。
Pulmonary hypertension is a chronic and chronic disease. The current research shows that the mechanism of pulmonary hypertension is not completely understood and may be closely related to genes, environment and dietary habits. Recent studies have shown that microRNAs (miRNAs) are directly or indirectly involved in the formation of pulmonary hypertension. MiR-143/145 expression was increased and miR-143/145-transcription factor (KLF4 / KLF5) -smooth muscle actin (SMA), calponin and SM22-alpha signaling pathways were increased, Leading to differentiation of smooth muscle cells (SMCs) while inhibiting their proliferation; similar to miR-143/145, miR-21 expression was increased and increased by miR-21-PPARα-SMA, calponin, SM22-α-SMC signaling pathway leads to SMC differentiation and inhibits SMC proliferation; miR-204 plays a role in miR-204-signal transducers and activators of transcription 3 (STAT3) -activated T cell nuclear factor (NFAT) , Eventually leading to vasoconstriction and proliferation of pulmonary artery smooth muscle cells (PASMC); miR-206 leads to altered mitochondrial function in the miR-206-hypoxia inducible factor 1α (HIF-1α) -424 / 503 - Fibroblast growth factor (FGF) 2 / FGFR1-mitogen-activated protein kinase signaling pathway (MAPK) -KLF2-endothelial nitric oxide synthase (eNOS) signaling pathway, leading to endothelial cells and SMC Hyperplasia. In addition, hypoxia leads to changes in miR-328 levels, which in turn affect the expression of L-type calcium channel-αC protein, leading to pulmonary hypertension. Because of its small molecular weight, miRNAs are easy to synthesize and modify and will be effective drugs for the treatment of pulmonary hypertension.