MicroRNA-7 Deficiency Ameliorates the Pathologies of Acute Lung Injury through Elevating KLF4

Zhao, Juanjuan; Chen, Chao; Guo, Ming; Tao, Yijing; Cui, Panpan; Zhou, Yue; Qin, Nalin; Zheng, Jing; Zhang, Ji Dong; Xu, Lin

doi:10.3389/fimmu.2016.00389

Cited by 42 publications

(61 citation statements)

References 63 publications

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“… reported that down‐regulation of miR‐451a affects the activation and proliferation of CD4 + T cells by targeting the transcription factor myelocytomatosis oncogene (Myc) in dilated cardiomyopathy (DCM) patients, which contribute to the immunopathogenesis of DCM. Our new research work also reports that miR‐7 deficiency alters the proportion and absolute number of CD4 + T cells in bronchoalveolar lavage (BAL), while it is related to ameliorated pathologies of acute lung injury . In the present study, we extend previous findings by demonstrating that miR‐126 deficiency could clearly elevate activation and proliferation, as well as IFN‐γ secretion, in CD4 + T cells, indicating that miR‐126 might be a novel negative factor in CD4 + T cell function.…”

Section: Discussionsupporting

confidence: 85%

MicroRNA-126 deficiency enhanced the activation and function of CD4+T cells by elevating IRS-1 pathway

Chu

Zhou

et al. 2017

Clinical and Experimental Immunology

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Recent evidence has shown that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4 T cells remains largely unknown. Here we first found that the activation and proliferation, as well as the expression of interferon (IFN)-γ, of CD4 T cells from miR-126 knock-down (KD) mice using the miRNA-sponge technique were enhanced significantly in vitro, compared with those in CD4 T cells from wild-type (WT) mice. To monitor further the possible effect of miR-126 deficiency on the function of CD4 T cells in vivo, we used dextran sulphate sodium (DSS)-induced murine model of acute autoimmune colitis and found that miR-126 deficiency could elevate the pathology of colitis. Importantly, the proportion of CD4 T cells in splenocytes increased significantly in miR-126KD mice. Moreover, the expression levels of CD69 and CD44 on CD4 T cells increased significantly and the expression level of CD62L decreased significantly. Of note, adoptive cell transfer assay showed that the pathology of colitis was more serious in carboxyfluorescein succinimidyl ester (CFSE)-labelled miR-126KD CD4 T cell-transferred group, compared with that in the CFSE-labelled WT CD4 T cells transferred group. Consistently, the expression levels of CD69 and CD44 on CFSE cells increased significantly. Furthermore, both the proliferation and IFN-γ secretion of CFSE cells also increased significantly in the CFSE-labelled miR-126KD CD4 T cell-transferred group. Mechanistic evidence showed that the expression of insulin receptor substrate 1 (IRS-1), as a functional target of miR-126, was elevated in CD4 T cells from miR-126KD mice, accompanied by altered transduction of the extracellular regulated kinase, protein B (AKT) and nuclear factor kappa B (NF-κB) pathway. Our data revealed a novel role in which miR-126 was an intrinsic regulator in the function of CD4 T cells, which provided preliminary basis for exploring further the role of miR-126 in the development, function of CD4 T cells and related clinical diseases.

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Section: Discussionsupporting

confidence: 85%

MicroRNA-126 deficiency enhanced the activation and function of CD4+T cells by elevating IRS-1 pathway

Chu

Zhou

et al. 2017

Clinical and Experimental Immunology

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“…Over the past decade, accumulative data have demonstrated that aberrant expression of miRNAs involved in the occurrence and development of ALI (Cai et al, ; Fang, Gao, Hao, & Liu, ). During ALI, the expression levels of miR‐7, miR‐582‐5p, miR‐582‐3p, miR‐450a‐3p, and miR‐29b are up‐regulated (Guo et al, ; Zhao et al, ), but the expression levels of miR‐125b, miR‐208a, miR‐133b, let‐7, miR‐34c are down‐regulated (Guo et al, ; Otsuki, Ishikawa, Hori, Goto, & Sakamoto, ). PGRN can be regulated by miRNAs in different physiological and pathological contexts (Jiao, Herl, Farese, & Gao, ; Qian et al, ).…”

Section: Discussionmentioning

confidence: 99%

miR‐34b‐5p inhibition attenuates lung inflammation and apoptosis in an LPS‐induced acute lung injury mouse model by targeting progranulin

Xie

Wang

et al. 2018

Journal Cellular Physiology

135

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Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS‐induced ALI. Here, we have investigated the potential roles of PGRN‐targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS‐induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR‐34b‐5p in ALI was determined by transfection of a miR‐34b‐5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT‐PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR‐34b‐5p levels were closely associated with PGRN expression in the lung homogenates. The gain‐ and loss‐of‐function analysis, dual‐luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR‐34b‐5p. Intravenous injection of miR‐34b‐5p antagomir in vivo significantly inhibited miR‐34b‐5p up‐regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR‐34b‐5p knockdown attenuates lung inflammation and apoptosis in an LPS‐induced ALI mouse model by targeting PGRN. This study shows that miR‐34b‐5p and PGRN may be potential targets for ALI treatments.

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“…To evaluate the cellular distribution of miR-7 in the tumors, in situ hybridization was performed according to our previous description 56 with some modifications. Briefly, before hybridization incubation, all solutions were prepared with diethyl pyrocarbonate-treated water.…”

Section: Methodsmentioning

confidence: 99%

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

Chen

Zhao

et al. 2017

Molecular Therapy - Nucleic Acids

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Targeted expression of gene technique is an important therapeutic strategy for lung cancer. MicroRNA-7 has been well documented as a promising tumor suppressor but never been test in specific gene-promoter-targeted expression in cancer gene therapy. Here, we first evaluated the efficacy of miR-7 expression operated by the promoter of TTF-1, a lineage-specific oncogene in lung cancer, in vitro using an eukaryotic vector of TTF-1-promoter-operated expression of miR-7 (termed as p-T-miR-7). Interestingly, using a nude mice model, the growth and metastasis of human lung cancer cells in vivo were significantly reduced in remote hypodermic injection of the p-T-miR-7 group, accompanied by increased expression of miR-7 and reduced transduction of the Akt and Erk pathway in situ. Mechanism aspect, global gene expression analysis showed that downregulation of NDUFA4, a novel target of miR-7, contributed to the effects of miR-7 expression operated by TTF-1 promoter on the growth and metastasis of human lung cancer cells, as well as altered transduction of the Akt and Erk pathway. Finally, there was no significant difference in weight or histopathology of other organs. These data provided a basis for development of novel modality of miRNA-based targeted expression therapy against clinical lung cancer.

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MicroRNA-7 Deficiency Ameliorates the Pathologies of Acute Lung Injury through Elevating KLF4

Cited by 42 publications

References 63 publications

MicroRNA-126 deficiency enhanced the activation and function of CD4+T cells by elevating IRS-1 pathway

MicroRNA-126 deficiency enhanced the activation and function of CD4+T cells by elevating IRS-1 pathway

miR‐34b‐5p inhibition attenuates lung inflammation and apoptosis in an LPS‐induced acute lung injury mouse model by targeting progranulin

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

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