MicroRNA Regulation of Macrophage Polarization in Muscle Regeneration
肌肉再生中巨噬细胞极化的 MicroRNA 调节
基本信息
- 批准号:8598034
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-10-01 至 2015-09-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdjuvantAdverse effectsAffectAfghanistanAmazeAmputationAnimalsAreaBiologicalBone MarrowBone Marrow CellsCC chemokine receptor 2Cell Differentiation processCell physiologyCell surfaceCellsChronicComplexDataDefectDevelopmentDiseaseEventGene ExpressionGoalsHealedHumanImmuneImpairmentIn VitroIndividualInflammationInflammatoryInjuryLeadLegLeukocytesLimb SalvageLimb structureMediatingMedicalMessenger RNAMicroRNAsModelingMusMuscleMuscle FibersNatural regenerationOligonucleotidesOutcomePatientsPopulationProcessProliferatingRNARecoveryRegulationResearchResolutionRoleSkeletal MuscleSkeletal muscle injurySkinSoldierStem cellsSurfaceSystemTestingTherapeuticTissue EngineeringTissuesTraumaTravelUntranslated RNAVeteransWarWild Type MouseWound Healingangiogenesisarmbasechemokinecombatcytokinedefined contributiondesignhealingimprovedin vivoinjuredinnovationlocked nucleic acidloss of functionmacrophagemonocytemouse modelmuscle regenerationnovelnovel therapeuticsregenerativeresearch studysatellite cellsoft tissuetissue regenerationtissue repairwound
项目摘要
DESCRIPTION (provided by applicant):
Stem cells and tissue regeneration have great therapeutic promise for treatment of a wide variety of medical conditions. For example and relevant to the current application, extremity injuries compromise 50-60% of all combat casualties observed in Iraqi/Afghanistan War Veterans resulting in large soft tissue defects (muscle and skin) and high amputation rates. Skeletal muscle, while being the tissue most vulnerable to ischemic damage in the extremities, also has an amazing potential to regenerate due to satellite cells. Satellite cells are stem cells that reside in skeletal muscle and with muscle injury, can proliferate and fuse together or with damaged muscle fibers to regenerate muscle; macrophages are critical to this process. Multiple types of macrophages participate in the regenerative process; classically activated (M1), wound healing (M2a) and regulatory (M2c) macrophage subsets are present in skin wounds and regenerating skeletal muscle; promoting inflammation, tissue repair and resolution of inflammation, respectively. However, the regulation of macrophage specialization (polarization) by microRNAs (miRNAs), and the consequential effects of macrophage subsets on muscle regeneration have not been elucidated. MiRNAs are small, noncoding RNAs that inhibit gene expression, thereby regulating many processes, including immune cell differentiation. A better understanding of the mechanisms of skeletal muscle regeneration and skin wound healing, and the influence of macrophage polarization on these events, could lead to new and adjunct therapies for limb salvage. Our long-term goal is to define the influence of inflammation, including the chemokine system, in angiogenesis, wound healing and skeletal muscle regeneration. We have extensively studied the importance of the CC Chemokine Receptor 2 (CCR2) in muscle regeneration. CCR2 is crucial for monocyte/macrophage recruitment and differentiation. Following muscle injury, CCR2-/- mice have impairments in macrophage recruitment, angiogenesis and muscle regeneration compared to wild type (WT) mice. Importantly, macrophage recruitment and muscle regeneration defects can be reversed in CCR2-/- mice by providing WT bone marrow, thus, CCR2 expression on bone marrow-derived cells is critical for normal muscle regeneration and macrophages are the likely BM-derived cell that mediates this outcome. The following 3 specific aims will be tested: 1) Define the in vitro regulation of macrophage polarization by selected miRNAs (miR-21 and -147). 2) Establish the mRNA targets of selected miRNAs (miR-21 and -147) during macrophage polarization and 3) Determine the biological effects of individual miRNAs on in vivo macrophage subsets and coordinated biological events during wound healing. By modulating macrophage polarization via increased or decreased miRNA expression, we seek to improve wound healing and decrease the adverse affects of acute and chronic inflammation present in many diseases that affect the Veteran population. The proposed studies are innovative because they will help define the contribution of miRNAs to macrophage polarization and subsequent muscle regeneration and wound healing. The combination of in vitro and in vivo studies will collectively identify miRNAs important for macrophage polarization, determine the mRNA targets, and assess any effects on muscle regeneration and wound healing. Given the availability of locked-nucleic-acid-modified oligonucleotide (LNA-antimiR), RNA oligonucleotides complementary to specific miRNAs that can be used in animals to decrease miRNA expression, a new therapeutic class of agents could become available for humans. The significance of this research is that a better understanding of the mechanisms of skeletal muscle regeneration and wound healing could lead to the design of novel primary or adjuvant treatments for improved limb salvage using miRNA- altering compounds.
描述(由申请人提供):
项目成果
期刊论文数量(0)
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PAULA K SHIREMAN其他文献
PAULA K SHIREMAN的其他文献
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{{ truncateString('PAULA K SHIREMAN', 18)}}的其他基金
Harnessing the power of CTSA-CDRN data networks: Using social determinants of health, frailty and functional status to identify at-risk patients and improve risk adjustment
利用 CTSA-CDRN 数据网络的力量:利用健康、虚弱和功能状态的社会决定因素来识别高危患者并改善风险调整
- 批准号:
10199784 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Harnessing the power of CTSA-CDRN data networks: Using social determinants of health, frailty and functional status to identify at-risk patients and improve risk adjustment
利用 CTSA-CDRN 数据网络的力量:利用健康、虚弱和功能状态的社会决定因素来识别高危患者并改善风险调整
- 批准号:
9981049 - 财政年份:2018
- 资助金额:
-- - 项目类别:
MicroRNA Regulation of Macrophage Polarization in Muscle Regeneration
肌肉再生中巨噬细胞极化的 MicroRNA 调节
- 批准号:
8240594 - 财政年份:2011
- 资助金额:
-- - 项目类别:
MicroRNA Regulation of Macrophage Polarization in Muscle Regeneration
肌肉再生中巨噬细胞极化的 MicroRNA 调节
- 批准号:
8391644 - 财政年份:2011
- 资助金额:
-- - 项目类别:
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