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2.
J Biol Chem ; 299(8): 104964, 2023 08.
Article in English | MEDLINE | ID: mdl-37364687

ABSTRACT

The epithelium of the pulmonary airway is composed of several distinct cell types that differentiate from common progenitor cells to provide defense against environmental insults. Epigenetic mechanisms regulating lineage differentiation of airway epithelial progenitors remain poorly understood. Protein arginine methyltransferase 5 (Prmt5) is a predominant type II arginine methyltransferase that methylates >85% of symmetric arginine residues. Here, we provide evidence for the function of Prmt5 in promoting ciliated cell fate specification of airway epithelial progenitors. We show that lung epithelial-specific deletion of Prmt5 resulted in a complete loss of ciliated cells, an increased number of basal cells, and ecotopic-expressed Tp63-Krt5+ putative cells in the proximal airway. We further identified that transcription factor Tp63 is a direct target of Prmt5, and Prmt5 inhibited Tp63 transcription expression through H4R3 symmetric dimethylation (H4R3sme2). Moreover, inhibition of Tp63 expression in Prmt5-deficient tracheal progenitors could partially restore the ciliated cell deficient phenotype. Together, our data support a model where Prmt5-mediated H4R3sme2 represses Tp63 expression to promote ciliated cell fate specification of airway progenitors.


Subject(s)
Gene Expression Regulation , Transcription Factors , Animals , Humans , Mice , Cell Differentiation , Cell Line, Tumor , Lung/metabolism , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Transcription Factors/metabolism , Mice, Inbred C57BL
3.
Oxid Med Cell Longev ; 2020: 8822361, 2020.
Article in English | MEDLINE | ID: mdl-33101593

ABSTRACT

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Acute Lung Injury/pathology , Calcium-Binding Proteins/metabolism , MicroRNAs/metabolism , AMP-Activated Protein Kinases/genetics , Acute Lung Injury/drug therapy , Animals , Antagomirs/metabolism , Antagomirs/therapeutic use , Blood Gas Analysis , Calcium-Binding Proteins/antagonists & inhibitors , Calcium-Binding Proteins/genetics , Disease Models, Animal , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/toxicity , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Oxidative Stress/drug effects , RNA Interference , RNA, Small Interfering/metabolism , Signal Transduction/drug effects , Superoxide Dismutase/metabolism , Up-Regulation/drug effects
4.
Sci Rep ; 10(1): 11184, 2020 07 07.
Article in English | MEDLINE | ID: mdl-32636440

ABSTRACT

Astragalus membranaceus (HUANG QI, HQ) is a kind of traditional Chinese medicine. Researchers have widely concerned its antitumor effect. At present, there is still a lack of research on the treatment of laryngeal cancer with HQ. In this study, we integrated data from the weighted gene co-expression network of laryngeal cancer samples and the components and targets of HQ. A new method for dividing PPI network modules is proposed. Important targets of HQ treatment for laryngeal cancer were obtained through the screening of critical modules. These nodes performed differential expression analysis and survival analysis through external data sets. GSEA enrichment analysis reveals pathways for important targets participation. Finally, molecular docking screened active ingredients in HQ that could interact with important targets. Combined with the laryngeal cancer gene co expression network and HQ PPI network, we obtained the critical module related to laryngeal cancer. Among them, MMP1, MMP3, and MMP10 were chosen as important targets. External data sets demonstrate that their expression in tumor samples is significantly higher than in normal samples. The survival time of patients with high expression group was significantly shortened, which is a negative factor for prognosis. GSEA enrichment analysis found that they are mainly involved in tumor-related pathways such as ECM receptor interaction and Small cell lung cancer. The docking results show that the components that can well bind to important targets of HQ are quercetin, rutin, and Chlorogenic acid, which may be the primary mechanism of the anti-cancer effect of HQ. These findings provide a preliminary research basis for Chinese medicine treatment of laryngeal cancer and offer ideas to related drug design.


Subject(s)
Antineoplastic Agents/pharmacology , Astragalus propinquus/chemistry , Drugs, Chinese Herbal/pharmacology , Gene Regulatory Networks , Laryngeal Neoplasms/genetics , Protein Interaction Maps , Antineoplastic Agents/chemistry , Drugs, Chinese Herbal/chemistry , Gene Expression Regulation, Neoplastic/drug effects , Humans , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/metabolism , Molecular Docking Simulation , Protein Binding/drug effects
5.
Mol Med Rep ; 22(2): 1458-1466, 2020 08.
Article in English | MEDLINE | ID: mdl-32626979

ABSTRACT

Acute lung injury (ALI) is a severe lung syndrome with high morbidity and mortality, due to its complex mechanism and lack of effective therapy. The use of placenta­derived mesenchymal stem cells (pMSCs) has provided novel insight into treatment options of ALI. The effects of pMSCs on lipopolysaccharide (LPS)­induced inflammation were studied using a co­culture protocol with LPS­stimulated RAW264.7 cells. An LPS­induced ALI Sprague­Dawley rat model was developed by intravenously injecting 7.5 mg/kg LPS, and intratracheal instillation of 1x105 pMSCs was performed after administration of LPS to investigate the therapeutic potential of these cells. pMSCs ameliorated LPS­induced ALI, as suggested by downregulated pro­inflammatory cytokine tumor necrosis factor­α and increased anti­inflammatory cytokine interleukin­10 in both cell and animal models. Moreover, the protein and leukocyte cells in bronchoalveolar lavage fluid decreased at a rapid rate after treatment with pMSCs. Histopathology demonstrated that pMSCs alleviated the infiltration of inflammatory cells, pulmonary hyperemia and hemorrhage, and interstitial edema. In addition, pMSC reduced the LPS­induced expression of C­X­C motif chemokine ligand 12 in RAW264.7 macrophages and in lung tissue of ALI rats. This demonstrated that pMSCs are therapeutically effective in LPS­induced ALI.


Subject(s)
Acute Lung Injury/therapy , Cytokines/metabolism , Inflammation/therapy , Lung/metabolism , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Acute Lung Injury/chemically induced , Animals , Coculture Techniques , Female , Inflammation/chemically induced , Lipopolysaccharides , Lung/pathology , Male , Mice , Placenta/cytology , Pregnancy , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley
6.
Inorg Chem ; 57(20): 12461-12465, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-30251837

ABSTRACT

In this work, we designed a hybrid catalyst composed of a metal-organic framework (MOF), Pt nanoparticles (NPs), and ferric oxide, namely, Co-MOF-74@(Pt@Fe2O3), which enables not only high turnover frequencies of up to 245.7 h-1 but also ultrahigh 100% selectivity toward cinnamyl alcohol in the hydrogenation of cinnamaldehyde under mild conditions. This excellent performance is attributed to the fact that such a hybrid catalyst enables not only strong steric constraint to provide the favored C═O adsorption of cinnamaldehyde but also strong metal-support interaction to lower the electron density of Pt NPs.

7.
Dalton Trans ; 46(2): 338-341, 2017 Jan 03.
Article in English | MEDLINE | ID: mdl-27957568

ABSTRACT

Reversible photo/thermoswitchable dual-color green-to-blue fluorescence is reported here, which is mainly due to a single-crystal-to-single-crystal (SCSC) transformation of the chromophore from a supramolecular aggregation to a covalently bonded polymer.

8.
Chem Commun (Camb) ; 52(61): 9538-41, 2016 Aug 07.
Article in English | MEDLINE | ID: mdl-27380820

ABSTRACT

Herein, we demonstrate that Zn-MOF-74 enables the ultrafast and one-step generation of the Fe2O3@MOF composite once Zn-MOF-74 contacts with FeSO4 solution. This unique reaction can be further applied in catalysis of U(vi) reduction by Fe(ii) under ambient conditions. The results provide a highly renovated strategy for U(vi) reduction by Fe(ii) just under ambient conditions, which completely subvert all established methods about U(vi) reduction by Fe(ii) in which O2- and CO2-free conditions are absolutely required.

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