Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models

Murdaca, Giuseppe; Tonacci, Alessandro; Negrini, Simone; Greco, Monica; Borro, Matteo; Puppo, Francesco; Gangemi, Sebastiano

emonstrating that Ant-17 and Ant-21 reduced right ventricular systolic pressure and pulmonary arterial muscularization. Moreover, Ant-17 decreased hypoxia-induced right ventricular hypertrophy and improved pulmonary artery acceleration time. In mice, Ant-17 therapy reduced right ventricular systolic pressure and total pulmonary vascular resistance index, stabilized cardiac output and reduced pulmonary vascular remodeling. In human pulmonary artery smooth muscle cells, Ant-17 increased the cyclin-dependent kinase inhibitor 1A (p21). MiRNA 21 demonstrated to have a role also upon lung fibrosis. In fact, Shentu et al. [26] demonstrated that human mesenchymal stem cell-derived extracellular vesicles (mEVs) do contain several specific miRNAs including 21-5p and 630. MEVs suppress TGFβ1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts, thus mitigating tissue fibrotic response. Investigating the role of miRNA regarding the pathogenesis and progression of lung fibrosis, Liu et al. [98] found that miR-21 was up-regulated both in the lungs of mice presenting with bleomycin-induced lung fibrosis and IPF patients. In this setting, miR-21 was highly expressed by myofibroblasts in the fibrotic lungs. Furthermore, researchers noticed that miR-21 reduced bleomycin-induced lung fibrosis in rats' lungs.