Biological Roles of Forkhead Box C1 in Pelvic Endometriosis
Biological Roles of Forkhead Box C1 in Pelvic Endometriosis
批准号:
10154109
负责人:
Gregory Willis Burns
金额:
$6.64万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-12-02 至 2022-01-02
关键词:
AffectAgeBiologicalChronicCicatrixDataDevelopmentDiagnosisDiagnostic ProcedureDiseaseDisease ProgressionEndometrialEndometriumEpithelialEpithelial CellsEstrogensEtiologyFOXC1 geneFemaleFertilityFibroblastsFibrosisFoundationsGATA6 transcription factorGene ExpressionGenesGenetic TranscriptionGoalsHealthHumanImpairmentInfertilityKnowledgeLaboratoriesLesionMediatingMesenchymalMicroRNAsModelingMolecularMyofibroblastNon-MalignantOnset of illnessPapioPathogenesisPathologyPathway interactionsPelvic PainPelvisPeritoneumPost-Transcriptional RegulationRegulationRegulator GenesResearchRoleStromal CellsSystemTestingTissuesTrainingTranscriptional RegulationUterusVariantWomanWorkbasecareerchronic pelvic paincohortdiagnostic biomarkerdifferential expressionendometriosisexperiencegain of functiongene repressionimprovedinsightnoninvasive diagnosisnovel diagnosticsreproductivereproductive tracttherapeutic targettranscription factortranscriptome sequencingtranscriptomics
中文摘要
项目摘要
子宫内膜异位症是一种慢性、雌激素依赖性妇科疾病,影响10-15%的育龄妇女
女性,其特征在于子宫外存在子宫内膜组织,主要是在子宫内,
盆腔腹膜,并导致盆腔疼痛和不孕。这项研究的长期目标是发现
控制子宫内膜异位症发病机制的分子机制,特别是纤维化,
非侵入性诊断和生育保留治疗。在女性中很难研究病变的病因,
从发病到诊断的8-11年的重大延误和疾病的变化
进展在过去的25年里,Fazleabas实验室已经将狒狒作为一个合适的模型,
检查增生性病变的建立和进展。FOXC 1被确定为主要的上游
与来自转录组学的匹配子宫内膜相比,病变中差异表达基因的调节因子
分析。FOXC 1功能获得性与组织重塑和纤维化机制相关,
假设对病变的潜在发病机制至关重要。因此,
FOXC 1的表达可能是纤维化病变中纤维化发展的重要因素。
我们假设,FOXC 1的增加,作为转录和转录后调节的结果,
改变上皮细胞和基质细胞的功能,促进异位子宫内膜纤维化。我们将确定
转录和转录后机制,调节FOXC 1的表达增加,
FOXC 1表达对上皮细胞间质转化(EMT)和细胞增殖的影响。
成纤维细胞到肌成纤维细胞(FMT)的转变,这两种成分有助于纤维化病变中的纤维化。
拟议的研究将为FOXC 1增加的调控和下游效应提供关键的见解。
表达以揭示纤维化病变中纤维化发病机制的关键机制。技术
从这些研究和职业培训的经验,我的赞助商和共同赞助商将准备我
成功的独立研究生涯,调查子宫内膜异位症和女性生殖系统疾病
以改善人类健康。
英文摘要
PROJECT SUMMARY
Endometriosis is a chronic, estrogen-dependent gynecological disorder affecting 10-15% of reproductive age
women which is characterized by the presence of endometrial tissue outside the uterus, predominantly in the
pelvic peritoneum, and resulting in pelvic pain and infertility. The long-term goal of this research is discovery of
molecular mechanisms governing the pathogenesis of endometriosis, particularly fibrosis, for development of
non-invasive diagnostics and fertility-sparing treatments. Lesion etiology is difficult to study in women because
of the significant delays of 8-11 years from the onset of disease to diagnosis and variations in disease
progression. Over the past 25 years the Fazleabas lab has developed the baboon as an appropriate model to
examine the establishment and progression of endometriotic lesions. FOXC1 was identified as a major upstream
regulator of differentially expressed genes in lesions compared to matched endometrium from transcriptomic
analyses. FOXC1 gain-of-function is associated with tissue remodeling and mechanisms of fibrosis, a hallmark
of endometriotic lesions hypothesized to be crucial to the underlying pathogenesis of lesions. Thus, increased
expression of FOXC1 may be an important contributor to the development of fibrosis in endometriotic lesions.
We hypothesize that increased FOXC1, as a consequence of transcriptional and post-transcriptional regulation,
alters the function of epithelial and stromal cells to promote fibrosis in the ectopic endometrium. We will determine
the transcriptional and post-transcriptional mechanisms that regulate the increased expression of FOXC1 in
endometriotic lesions (Aim 1), and the effects of FOXC1 expression on epithelial to mesenchymal (EMT) and
fibroblast to myofibroblast (FMT) transitions, two components that contribute to fibrosis in endometriotic lesions.
The proposed studies will provide key insight into the regulation and downstream effects of increased FOXC1
expression to uncover critical mechanisms in the pathogenesis of fibrosis in endometriotic lesions. The technical
experience from these studies and career training from my sponsor and co-sponsors will prepare me for a
successful independent research career for investigating endometriosis and disorders of the female reproductive
tract to improve human health.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
国内基金
海外基金
登录
查看更多内容
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
-
批准号:JCZRLH202601523
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
-
批准号:JCZRQN202500010
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:
-
依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
-
批准号:2025JJ70209
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:雷芬芳
-
依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
-
批准号:--
-
项目类别:面上项目
-
资助金额:--
-
批准年份:2024
-
负责人:万荣
-
依托单位:
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
-
批准号:2023JJ50274
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2023
-
负责人:贺志明
-
依托单位:
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:33万元
-
批准年份:2022
-
负责人:都义日
-
依托单位:
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
-
批准号:--
-
项目类别:面上项目
-
资助金额:52万元
-
批准年份:2022
-
负责人:叶宝东
-
依托单位:
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:10.0万元
-
批准年份:2022
-
负责人:于海兵
-
依托单位:
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
-
批准号:81973577
-
项目类别:面上项目
-
资助金额:55.0万元
-
批准年份:2019
-
负责人:辛贵忠
-
依托单位:
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
-
批准号:81602908
-
项目类别:青年科学基金项目
-
资助金额:18.0万元
-
批准年份:2016
-
负责人:刘括
-
依托单位: