MicroRNA-7 deficiency ameliorates the pathologies of Acute Lung Injury through Elevating KLF4

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  Recent evidence showed that microRNA-7 (miR-7)played important roles in the pathologies of lung-related diseases including lung cancer.However, the potential role of miR-7 in acute lung injury(ALI) remains poorly understood.Here we assessed the effect of miR-7 deficiency on the pathology of ALI by using a murine ALI model.We firstly found that the expression of miR-7 was upregulated in lung tissues in murine LPS-induced ALI model.Notably, we further generated miR-7 knock down(KD) mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathology of lung as evidenced by accelerated body recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and reduced number of BAL cells in ALI mice.Moreover, the proportion and number of various immune cells in BAL, such as innate immune cell F4/80 + macrophages, γδT cells, NK1.1 + T cells and CD11 c+ DC cells, as well as adaptive immune cell CD4 + T cells and CD8 + T cells, also changed respectively.Mechanistic evidence showed that KLF4, a target molecule of miR-7 ,was upregulated in lung tissues in ALI model, accompanied by altered transduction of NF-B, AKT and ERK pathway.These data provided a previously unknown role of miR-7 in pathology of ALI, which could ultimately aid the understanding of development of ALI and the development of new therapeutic strategies against clinical inflammatory lung disease.
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