REST/NRSF, miRNAs, and tissue remodeling in adenomyosis pathophysiology
子宫腺肌症病理生理学中的 REST/NRSF、miRNA 和组织重塑
基本信息
- 批准号:10617304
- 负责人:
- 金额:$ 63.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-09 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:3&apos Untranslated RegionsAdenomyosisBiologicalBiological AssayCell CommunicationCell ProliferationCellsClinicalDataDevelopmentDiagnosisDiseaseDisease ProgressionEndometrialEndometriumEpithelial CellsEventExperimental ModelsFunctional disorderGene ExpressionGlandHormonalHumanHysterectomyImageIn VitroInvadedKnockout MiceKnowledgeMediatingMediatorMenstruationMicroRNAsMyometrialNeuronsNon-MalignantOutcome StudyPainPathogenesisPathologicPathway interactionsPelvic PainPrognostic MarkerProliferatingRE1-silencing transcription factorRegulationReporterReportingRepressionResearchRestRoleSeriesSignal PathwaySmooth MuscleSpecimenTestingTissuesTranscription RepressorUncertaintyUterine DiseasesUterusWomanWomen&aposs Groupcell motilityconditional knockoutdiagnostic biomarkereffective therapyendometrial stromaexperimental studyin vitro Modelinnovationinsightmigrationmouse modelmyometriumnoveloptimal treatmentsreproductivestemtheoriestissue injurytissue repairtranscription factortranscription factor RESTtranscriptome sequencingyoung woman
项目摘要
Project Summary
Adenomyosis is a nonmalignant uterine disease characterized by endometrial stroma and glands found
within the myometrium. Adenomyosis has been associated with heavy and painful menstrual periods, pelvic
pain, pain with intercourse, and reproductive dysfunction. However, now that imaging is identifying
adenomyosis in younger and more varied women than those electing hysterectomy where pathological
diagnosis occurred, many of our assumptions about the clinical disease are changing. Additionally, the only
widely accepted and effective treatments for adenomyosis, hysterectomy and hormonal suppression, are
unacceptable for this wider group of women. Much of our uncertainty on diagnosis and treatment for
adenomyosis stem from our uncertainty on its' pathogenesis. The most common theory of adenomyosis
development centers on the involvement of tissue injury and repair mechanisms with resulting adenomyosis
development from invagination of the endometrial basalis into the myometrium (the invasion/invagination
theory). While emerging data support a role for this theory and the involvement of cell migration, proliferation
and invasion in adenomyosis development, a detailed understanding on the mediators and mechanisms is
clearly lacking. To fill this critical gap in our knowledge we will perform a series of experiments which integrate
well-defined human specimens, novel mouse models and rigorous in vitro approaches to identify key
components of a REST-miRNA-tissue remodeling cascade and demonstrate the functionality of this pathway in
the pathogenesis of adenomyosis. The specific hypothesis to be tested in this application is that reduced
expression of endometrial and/or myometrial REST induces alterations in a miRNA-mediated tissue
remodeling cascade which augments adenomyosis development. To test this hypothesis, we will delineate
expression of a novel REST-miRNA mediated tissue remodeling pathway in adenomyosis and define REST's
function using novel experimental mouse models. Using in vitro models for cell proliferation, migration and
invasion, we will decipher cell to cell communication between myometrial-endometrial REST-miRNA tissue
remodeling pathway signaling relevant to adenomyosis pathophysiology. Together, these experiments will
provide novel insight into the role of REST in adenomyosis development and in turn, may lead to identification
of novel treatment targets for this disease.
项目总结
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Uterine Leiomyomas.
口服促性腺激素释放激素拮抗剂用于治疗子宫平滑肌瘤。
- DOI:10.1097/aog.0000000000005145
- 发表时间:2023
- 期刊:
- 影响因子:7.2
- 作者:Neblett2nd,MichaelF;Stewart,ElizabethA
- 通讯作者:Stewart,ElizabethA
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Vargheese Mani Chennathukuzhi其他文献
Vargheese Mani Chennathukuzhi的其他文献
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{{ truncateString('Vargheese Mani Chennathukuzhi', 18)}}的其他基金
REST/NRSF, miRNAs, and tissue remodeling in adenomyosis pathophysiology
子宫腺肌症病理生理学中的 REST/NRSF、miRNA 和组织重塑
- 批准号:
10277800 - 财政年份:2021
- 资助金额:
$ 63.62万 - 项目类别:
Allosteric CDK2 inhibitor Discovery and Development for Male Contraception
用于男性避孕的变构 CDK2 抑制剂的发现和开发
- 批准号:
10018520 - 财政年份:2019
- 资助金额:
$ 63.62万 - 项目类别:
Small molecule GPR10 antagonists for the treatment of uterine fibroids
小分子 GPR10 拮抗剂治疗子宫肌瘤
- 批准号:
9759969 - 财政年份:2018
- 资助金额:
$ 63.62万 - 项目类别:
Cell-cycle regulatory kinases as targets for male contraceptive drug development
细胞周期调节激酶作为男性避孕药物开发的靶点
- 批准号:
9253022 - 财政年份:2014
- 资助金额:
$ 63.62万 - 项目类别:
The role of REST in the pathogenesis of uterine fibroids
REST在子宫肌瘤发病机制中的作用
- 批准号:
9055746 - 财政年份:2013
- 资助金额:
$ 63.62万 - 项目类别:
The role of REST in the pathogenesis of uterine fibroids
REST在子宫肌瘤发病机制中的作用
- 批准号:
9261556 - 财政年份:2013
- 资助金额:
$ 63.62万 - 项目类别:
The role of REST in the pathogenesis of uterine fibroids
REST在子宫肌瘤发病机制中的作用
- 批准号:
8720039 - 财政年份:2013
- 资助金额:
$ 63.62万 - 项目类别:
The role of REST in the pathogenesis of uterine fibroids
REST在子宫肌瘤发病机制中的作用
- 批准号:
8596606 - 财政年份:2013
- 资助金额:
$ 63.62万 - 项目类别:
H2-Gamendazole analogues as reversible non-hormonal male contraceptive agents
H2-甘孟唑类似物作为可逆非激素男性避孕药
- 批准号:
9127311 - 财政年份:2012
- 资助金额:
$ 63.62万 - 项目类别:
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