Paracrine Regulation of Benign Prostate Hyperplasia Pathogenesis
良性前列腺增生发病机制的旁分泌调节
基本信息
- 批准号:7221941
- 负责人:
- 金额:$ 25.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-04-15 至 2009-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdolescentAdrenergic AntagonistsAdrenergic alpha-AntagonistsAdultAgingApoptosisBenignBenign Prostatic HypertrophyBiologicalBladderCombined Modality TherapyConditionDevelopmentDisease regressionDoxazosinEpithelialEpithelial-Stromal CommunicationFinasterideGlandGonadal Steroid HormonesGrowthHealth Care CostsHomeostasisHumanHyperplasiaInterventionLigandsMalignant - descriptorMedicalModelingMorbidity - disease rateNational Institute of Diabetes and Digestive and Kidney DiseasesNumbersObstructionOperative Surgical ProceduresOxidoreductasePathogenesisPathologyPathway interactionsPatientsPharmaceutical PreparationsPhenotypePlayProcessProstateProstaticProstatic EpitheliumProstatic StromaProstatic TissueProtein OverexpressionProteinsRandomizedRegulationRoleScoreSignal PathwaySignal TransductionSignaling MoleculeSmooth MuscleStromal CellsSymptomsThinkingTissue RecombinationTissuesTransforming Growth Factor betaWorkXenograft Modelbody systemconceptcostdesignfetalhormone regulationin vivoinhibitor/antagonistinsightmennew growthparacrinereceptor
项目摘要
DESCRIPTION (provided by applicant): The long-term objective of the work proposed in this project is to provide a firm groundwork of biological information allowing an understanding of the processes involved in the normal and pathological growth of the human prostate in vivo. The central hypothesis of this application is that paracrine interactions between the epithelial and stromal compartments of the prostate are responsible for BPH pathogenesis. The transforming growth factor-betas (TGFbeta) and their receptors (TGFbeta-R) are implicated in the regulation of proliferation and apoptosis in the prostatic epithelium. TGFbeta is also thought to be involved in the differentiation of a smooth muscle phenotype in the prostatic stroma. We will examine the expression and role of TGFbeta ligands, receptors and downstream activation of the TGFbeta signaling pathway in human prostatic tissue. We will then examine the effects of selectively either deleting expression or controllably over expressing these proteins in human prostatic tissue in vivo to determine their effects on epithelial and stromal differentiation and thus determine their ability to regulate prostatic pathology. The focus of this work is to demonstrate the mechanistic role, which TGFbeta signaling plays in maintaining adult homeostasis by regulating paracrine interactions between epithelial and stromal cells, and how inappropriate changes in such signaling might mimic BPH. The following specific aims will be pursued: Specific Aim 1: Expression and sex steroid hormone regulation of TGFbeta signaling molecules in developing, normal adult and hyperplastic adult human prostatic tissue. Specific Aim 2: Effects on downstream signaling pathways of controlled overexpression of TGFbeta signaling in growing, growth-quiescent, and regressing human prostatic tissue in vivo. Specific Aim 3: Controlled deletion of TGFbeta signaling in growing, growth-quiescent, and
regressing human prostatic tissue in vivo, mechanistic effects.
描述(由申请人提供):本项目中提出的工作的长期目标是提供生物信息的坚实基础,从而了解人体前列腺体内正常和病理生长过程。 本申请的中心假设是前列腺的上皮和基质区室之间的旁分泌相互作用是BPH发病机制的原因。 转化生长因子β(TGF β)及其受体(TGF β-R)参与前列腺上皮细胞增殖和凋亡的调节。TGF β也被认为参与前列腺基质中平滑肌表型的分化。 我们将研究TGF β配体,受体和TGF β信号通路在人前列腺组织中的下游激活的表达和作用。 然后,我们将研究选择性地删除表达或可控地过表达这些蛋白质在体内人前列腺组织中的影响,以确定它们对上皮和基质分化的影响,从而确定它们调节前列腺病理学的能力。 这项工作的重点是证明的机制作用,TGF β信号在维持成人稳态调节上皮细胞和基质细胞之间的旁分泌相互作用,以及如何在这种信号的不适当的变化可能模仿BPH。 具体目标1:TGF β信号分子在发育中、正常成人和增生成人人前列腺组织中的表达和性类固醇激素调节。 具体目标二:体内生长、生长-静止和退化的人前列腺组织中TGF β信号传导受控过表达对下游信号传导途径的影响。 具体目标3:生长、生长-静止和生长期TGF β信号转导的受控缺失
在体内使人前列腺组织退化,机械作用。
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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Simon W Hayward其他文献
MP35-02 <strong>BENIGN PROSTATIC HYPERPLASIA AND AUTOIMMUNE INFLAMMATORY DISEASES COINCIDENCE AND CONSEQUENCES</strong>
- DOI:
10.1016/j.juro.2016.02.1594 - 发表时间:
2016-04-01 - 期刊:
- 影响因子:
- 作者:
Jaclyn Pruitt;Jacqueline Petkewicz;Brittany Lapin;Omar E Franco;Brian T. Helfand;Charles B. Brendler;Chi-Hsiung Wang;Simon W Hayward - 通讯作者:
Simon W Hayward
MP62-14 ACTIVATION OF ABERRANT ANDROGEN RECEPTOR SIGNALING IN CARCINOMA ASSOCIATED FIBROBLASTS INDUCES PROSTATE CANCER PROGRESSION
- DOI:
10.1016/j.juro.2016.02.922 - 发表时间:
2016-04-01 - 期刊:
- 影响因子:
- 作者:
Omar E Franco;Rodrigo Javier;Susan E Crawford;Gustavo E Ayala;Simon W Hayward - 通讯作者:
Simon W Hayward
Simon W Hayward的其他文献
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{{ truncateString('Simon W Hayward', 18)}}的其他基金
Leukocytic Phenotypes Associated with BPH Progression
与 BPH 进展相关的白细胞表型
- 批准号:
9789816 - 财政年份:2018
- 资助金额:
$ 25.2万 - 项目类别:
AP-1 Factors in the Pathogenesis and Progression of Benign Prostatic Hyperplasia
AP-1在良性前列腺增生发病机制和进展中的影响因素
- 批准号:
8782874 - 财政年份:2014
- 资助金额:
$ 25.2万 - 项目类别:
AP-1 Factors in the Pathogenesis and Progression of Benign Prostatic Hyperplasia
AP-1在良性前列腺增生发病机制和进展中的影响因素
- 批准号:
9136661 - 财政年份:2014
- 资助金额:
$ 25.2万 - 项目类别:
AP-1 Factors in the Pathogenesis and Progression of Benign Prostatic Hyperplasia
AP-1在良性前列腺增生发病机制和进展中的影响因素
- 批准号:
8891421 - 财政年份:2014
- 资助金额:
$ 25.2万 - 项目类别:
AP-1 Factors in the Pathogenesis and Progression of Benign Prostatic Hyperplasia
AP-1在良性前列腺增生发病机制和进展中的影响因素
- 批准号:
9316616 - 财政年份:2014
- 资助金额:
$ 25.2万 - 项目类别:
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