Role of miRNA for the regulation of macrophage metabolism and phenotype determination in inflammatory disease
miRNA 在炎症性疾病中调节巨噬细胞代谢和表型决定的作用
基本信息
- 批准号:10056635
- 负责人:
- 金额:$ 24.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-19 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAdaptor Signaling ProteinAnti-Inflammatory AgentsAutoimmune DiseasesBiochemistryBiologicalBiological ProcessCellsCellular Metabolic ProcessDataDevelopmentDiseaseEnzymesFatty AcidsGene ExpressionGene Expression RegulationGenesGeneticGlycolysisGoalsHost DefenseImiquimodImmuneImmune responseInfectionInflammationInflammatoryInflammatory ResponseInvestigationLeukocytesLibrariesLinkMacrophage ActivationMeasuresMediatingMetabolismMicroRNAsMolecularMolecular BiologyMolecular TargetNatural ImmunityOxidative PhosphorylationPathologyPhagocytosisPhenotypePlayProcessProteinsPsoriasisRegulationRoleSLC2A1 geneSignal PathwaySignal TransductionSkinSmall RNASubfamily lentivirinaeTNF geneTestingTherapeuticTissuesUntranslated RNAbasecytokinefatty acid oxidationimmune activationin vivoinsightmacrophagemembermicrobialmouse modelnew therapeutic targetnovelresponsescreeningselective expressiontherapeutic evaluationtissue repairtranscription factortreatment strategytumor
项目摘要
ABSTRACT
Macrophages play a critical role in inflammation, systemic metabolism, tissue repair, host defense to
microbial infection, and tumor surveillance. Emerging evidence shows that pro-inflammatory macrophages rely
on glycolysis and fatty acid synthesis for the expression of pro-inflammatory genes, while anti-inflammatory
macrophages require oxidative phosphorylation and fatty acid oxidation for anti-inflammation gene expression,
suggesting that distinct aspects of cell metabolism regulate macrophage activation and polarization.
MicroRNAs (miRNAs) are a novel class of small noncoding RNA regulators that control gene expression.
Many miRNAs are selectively expressed in immune cells, and have been implicated in immune responses in
host defense and autoimmune disease. Recent findings indicate that miRNAs are involved in fundamental
macrophage functions by regulating cell metabolism. However, it is not clear how miRNAs regulate cell
metabolism for macrophage activation and inflammatory phenotype determination.
Using a lentivirus-based miRNA library that can reduce the inconsistency that occurs during the miRNA
profiling process, we selected miRNAs that regulate inflammatory responses in macrophages and that have
not been identified as regulators of metabolism and macrophage activation. Our long-term goal is revealing the
role of miRNAs for the functional association of miRNAs with macrophage metabolism and phenotype
determination, and applying that understanding for the treatment of inflammatory disease. miR-22, one of the
miRNA candidates from the screening process, regulates the expression of 4-1BBL, a member of the TNF
superfamily, and glucose transporter 1 (Glut1) in glycolysis during macrophage activation. However, it is not
clear how miR-22 regulates the expression of 4-1BBL and Glut1 in macrophage activation in inflammatory
disease. To investigate this, we hypothesize that miR-22 regulates the expression of 4-1BBL and Glut1 for the
regulation of sustained inflammation in macrophages, dysregulation of which contributes to the pathology of
psoriasis. We will examine the mechanism of miR-22-dependent regulation of macrophage metabolism and
phenotype determination by using biochemistry and molecular biology approaches such as analysis of the
signaling pathways and measuring cell metabolism (Aim 1) and study the role of miR-22 in inflammatory
diseases and its therapeutic potential using a mouse model of imiquimod-induced psoriasis-like skin
inflammation to test whether miR-22 administration can alleviate the pathology of psoriasis (Aim 2).
Understanding the importance of miRNA in the regulation of macrophage metabolism will elucidate novel
regulatory mechanisms in macrophage activation and phenotype determination in the development of
inflammatory diseases. Our exploration of a previously unattended function and control mechanism of miRNAs
in the regulation of cell metabolism will provide new translational insights about innate immunity in
inflammatory disease development and treatment.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Young Jun Kang其他文献
Improvement of labyrinth seal performance using the partial honeycomb lands
利用部分蜂窝状密封齿提高迷宫密封性能
- DOI:
10.1016/j.ast.2024.109082 - 发表时间:
2024-05-01 - 期刊:
- 影响因子:5.800
- 作者:
Hyeok Je Kim;Young Jun Kang;Woojun Kim;Won Seok Lim;Suhyeon Park;Jae Su Kwak - 通讯作者:
Jae Su Kwak
Effects of trench configuration on the film cooling effectiveness of a fan-shaped hole
- DOI:
10.1016/j.ijheatmasstransfer.2021.121655 - 发表时间:
2021-10-01 - 期刊:
- 影响因子:
- 作者:
Yu Jin Song;Sang Hyeon Park;Young Jun Kang;Jae Su Kwak - 通讯作者:
Jae Su Kwak
Generation and characterization of a novel tetravalent bispecific antibody that binds to hepatitis B virus surface antigens.
与乙型肝炎病毒表面抗原结合的新型四价双特异性抗体的生成和表征。
- DOI:
10.1016/s0161-5890(01)00027-x - 发表时间:
2000 - 期刊:
- 影响因子:3.6
- 作者:
Sung Sup Park;Chun Jeih Ryu;Young Jun Kang;S. Kashmiri;Hyo Jeong Hong - 通讯作者:
Hyo Jeong Hong
Effect of an inlet keyhole slot geometry on crossflow-fed-film cooling hole
进气锁眼槽几何形状对横流供液膜冷却孔的影响
- DOI:
10.1016/j.ijthermalsci.2025.109979 - 发表时间:
2025-09-01 - 期刊:
- 影响因子:5.000
- 作者:
Won Seok Lim;Young Jun Kang;Suhyeon Park;Jae Su Kwak - 通讯作者:
Jae Su Kwak
Expression, purification and characterization of soluble human thrombopoietin receptor from Escherichia coli
- DOI:
10.1023/a:1005672824663 - 发表时间:
2000-10-01 - 期刊:
- 影响因子:2.100
- 作者:
Heungrok Park;Hana Im;Young Jun Kang;Myeong-Hee Yu;Hyo Jeong Hong - 通讯作者:
Hyo Jeong Hong
Young Jun Kang的其他文献
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{{ truncateString('Young Jun Kang', 18)}}的其他基金
Role of miRNA for the regulation of macrophage metabolism and phenotype determination in inflammatory disease
miRNA 在炎症性疾病中调节巨噬细胞代谢和表型决定的作用
- 批准号:
10198739 - 财政年份:2020
- 资助金额:
$ 24.38万 - 项目类别:
Mechanism of 4-1BBL-mediated sustained inflammation: target of anti-inflammation
4-1BBL介导的持续炎症机制:抗炎靶点
- 批准号:
8260242 - 财政年份:2010
- 资助金额:
$ 24.38万 - 项目类别:
Mechanism of 4-1BBL-mediated sustained inflammation: target of anti-inflammation
4-1BBL介导的持续炎症机制:抗炎靶点
- 批准号:
8645596 - 财政年份:2010
- 资助金额:
$ 24.38万 - 项目类别:
Mechanism of 4-1BBL-mediated sustained inflammation: target of anti-inflammation
4-1BBL介导的持续炎症机制:抗炎靶点
- 批准号:
8454504 - 财政年份:2010
- 资助金额:
$ 24.38万 - 项目类别:
Mechanism of 4-1BBL-mediated sustained inflammation: target of anti-inflammation
4-1BBL介导的持续炎症机制:抗炎靶点
- 批准号:
8069245 - 财政年份:2010
- 资助金额:
$ 24.38万 - 项目类别:
Mechanism of 4-1BBL-mediated sustained inflammation: target of anti-inflammation
4-1BBL介导的持续炎症机制:抗炎靶点
- 批准号:
7992860 - 财政年份:2010
- 资助金额:
$ 24.38万 - 项目类别: