Tissue mechanics in regenerative wound healing of the skin
皮肤再生伤口愈合中的组织力学
基本信息
- 批准号:10217187
- 负责人:
- 金额:$ 31.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AccidentsAcomysAdipose tissueAdultAgeAmbystomaAmputationAtomic Force MicroscopyBasement membraneBioinformaticsBiosensorC57BL/6 MouseCell ShapeCellsChemicalsCicatrixConnective TissueDataDepositionDermalDermisDevelopmentDouble-Stranded RNAElementsEmbryonic DevelopmentEnvironmentEpidermisEpigenetic ProcessEpithelialEpithelial CellsEventExcisionExhibitsExtracellular MatrixFGF9 geneFetusFluorescence Resonance Energy TransferFutureGenesGenomeHairHair follicle structureInflammatory ResponseIntrinsic factorKnockout MiceLaboratoriesLaboratory miceLearningMapsMechanicsModelingMolecularMusNamesNatural regenerationNatureNewborn InfantOutcomePatientsPhysical condensationPlayProcessRegenerative MedicineRegulationRoleSignal TransductionSiteSkinSkin wound healingSomatic CellSpatial DistributionTestingTissuesWorkappendagebeta cateninblastemafunctional restorationhealingimprovedmechanotransductionmorphogensnew therapeutic targetnovelprogenitorprogrammed cell death protein 1regenerativerepairedreparative healingresponseshape analysisskin woundstem cellstissue regenerationtissue repairtongue papillatumorwoundwound bedwound closurewound environmentwound healingwound treatment
项目摘要
Summary
Our long term objective is to heal skin wounds with full functional restoration
(regenerative wound healing) instead of scarring (reparative wound healing). We aspire to learn
what factors control regeneration as supposed to repair during wound healing under the newly
established paradigm of “Wound-Induced Hair Neogenesis” (WIHN). In this model, new hair
follicles emerge from the wound center when a large (>1cm) skin wound is made on the mice
(e.g., C57BL/6). Our new finding in Spiny mice (Acomys) shows, however, that WIHN starts to
form from the periphery of wounds toward the center. Our preliminary data further shows a
distinct spatial distribution of mechanical stiffness across the wound field, and that perturbation
of mechanotransduction in the wound bed alters the outcome of WIHN. These new findings
prompted us to hypothesize that tissue mechanics modulate tissue regeneration and WIHN.
WIHN is easily accessible and is a good model to evaluate this hypothesis. While epithelial
placode formation can be initiated by different chemical morphogens present during embryonic
development (which converge to induce beta-catenin signaling), in WIHN of both C57BL/6 and
spiny mouse, the mechanical environment of the wound can modulate, in parallel or
independently, the threshold of successful placode formation. This acts to alter the status of
epithelia activation, basement membrane remodeling, and dermal condensation. In Aim 1A, we
will compare the different cellular and molecular events leading to WIHN, contrasting spiny and
C57BL/6 mice. Supported by the bioinformatic analyses, Twist1 is proposed as a master
regulator for placode formation in the spiny mouse. Therefore, the role of Twist1 and its
downstream Msx2 in WIHN will be examined in Aim1B. In Aim 2A, we will map the stiffness in
different parts of the wound field employing atomic force microscopy accompanied by cell shape
analyses and FRET-biosensors to indirectly “visualize” the consequence of cell forces within the
wound site. The role of tissue mechanics in WIHN will be further tested by perturbation studies.
Aim 2B will investigate and define the molecular circuits which are functioning in the conductive
mechanical environment for placode regeneration. Overall, the proposal aims to explore novel
epidermal-dermal networks during regenerative wound healing from the perspective of
epigenetic, molecular, and mechanical inputs that construct the grand theme of elements
necessary for future progression of regenerative medicine.
!
总结
我们的长期目标是治愈皮肤伤口,并恢复完整的功能
(再生性伤口愈合)而不是瘢痕形成(修复性伤口愈合)。我们渴望学习
什么因素控制再生,因为应该在伤口愈合过程中修复,
建立了“创伤诱导毛发新生”(WIHN)的范例。在这个模型中,
当在小鼠上造成大的(>1cm)皮肤伤口时,毛囊从伤口中心出现
(e.g., C57BL/6)。然而,我们在刺鼠(Acomys)中的新发现表明,WIHN开始
从伤口的边缘向中心形成。我们的初步数据进一步显示,
在整个伤口领域的机械刚度的独特的空间分布,
在创伤床中的机械传导改变了WIHN的结果。这些新发现
提示我们假设组织力学调节组织再生和WIHN。
WIHN很容易获得,并且是评估这一假设的良好模型。虽然上皮
基板的形成可由胚胎发育期间存在的不同化学形态发生素启动
在C57 BL/6和C57 BL/6的WIHN中,
在多刺小鼠中,伤口的机械环境可以平行或平行地调节,
独立地,成功基板形成的阈值。这会改变
上皮活化、基底膜重塑和真皮冷凝。在目标1A中,我们
将比较导致WIHN的不同细胞和分子事件,对比多刺和
c57 bl/6小鼠在生物信息学分析的支持下,Twist 1被认为是一个主因子
多刺小鼠基板形成的调节因子。因此,Twist 1的作用及其
将在Aim 1B中检查WIHN中的下游Msx 2。在目标2A中,我们将刚度映射到
采用原子力显微镜观察伤口不同部位的细胞形态
分析和FRET-生物传感器,以间接“可视化”细胞内的细胞力的结果,
伤口部位组织力学在WIHN中的作用将通过微扰研究进一步测试。
目标2B将研究和定义在导电介质中起作用的分子电路。
基板再生的机械环境。总体而言,该提案旨在探索新的
表皮-真皮网络在再生伤口愈合过程中的作用
表观遗传、分子和机械输入,构成了元素的宏大主题
这是再生医学未来发展的必要条件。
!
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tissue Mechanics in Haired Murine Skin: Potential Implications for Skin Aging.
- DOI:10.3389/fcell.2021.635340
- 发表时间:2021
- 期刊:
- 影响因子:5.5
- 作者:Harn HI;Chen CC;Wang SP;Lei M;Chuong CM
- 通讯作者:Chuong CM
Skin Cyst: A Pathological Dead-End With a New Twist of Morphogenetic Potentials in Organoid Cultures.
- DOI:10.3389/fcell.2020.628114
- 发表时间:2020
- 期刊:
- 影响因子:5.5
- 作者:Qiu W;Gu PR;Chuong CM;Lei M
- 通讯作者:Lei M
Epidermal Darwinism and Competitive Equilibrium within the Epidermis.
- DOI:10.1016/j.stem.2018.10.019
- 发表时间:2018-11-01
- 期刊:
- 影响因子:23.9
- 作者:Lei M;Chuong CM
- 通讯作者:Chuong CM
Human Fetal Scalp Dermal Papilla Enriched Genes and the Role of R-Spondin-1 in the Restoration of Hair Neogenesis in Adult Mouse Cells.
- DOI:10.3389/fcell.2020.583434
- 发表时间:2020
- 期刊:
- 影响因子:5.5
- 作者:Weber EL;Lai YC;Lei M;Jiang TX;Chuong CM
- 通讯作者:Chuong CM
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Cheng-Ming Chuong其他文献
Cheng-Ming Chuong的其他文献
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{{ truncateString('Cheng-Ming Chuong', 18)}}的其他基金
Tissue mechanics in regenerative wound healing of the skin
皮肤再生伤口愈合中的组织力学
- 批准号:
9546436 - 财政年份:2018
- 资助金额:
$ 31.35万 - 项目类别:
Tissue mechanics in regenerative wound healing of the skin
皮肤再生伤口愈合中的组织力学
- 批准号:
9755462 - 财政年份:2018
- 资助金额:
$ 31.35万 - 项目类别:
Training in Developmental Biology, Stem cells and Regeneration
发育生物学、干细胞和再生培训
- 批准号:
8660702 - 财政年份:2011
- 资助金额:
$ 31.35万 - 项目类别:
Training in Developmental Biology, Stem cells and Regeneration
发育生物学、干细胞和再生培训
- 批准号:
8469066 - 财政年份:2011
- 资助金额:
$ 31.35万 - 项目类别:
Training in Developmental Biology, Stem cells and Regeneration
发育生物学、干细胞和再生培训
- 批准号:
8253753 - 财政年份:2011
- 资助金额:
$ 31.35万 - 项目类别:
Training in Developmental Biology, Stem cells and Regeneration
发育生物学、干细胞和再生培训
- 批准号:
8847752 - 财政年份:2011
- 资助金额:
$ 31.35万 - 项目类别:
Training in Developmental Biology, Stem cells and Regeneration
发育生物学、干细胞和再生培训
- 批准号:
8078789 - 财政年份:2011
- 资助金额:
$ 31.35万 - 项目类别:
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