Effects of force and hormonal environment on cervical matrix

力和荷尔蒙环境对宫颈基质的影响

• 批准号: 8110639
• 负责人: EDWARD K CHIEN
• 金额: $ 7.12万
• 依托单位: WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110639
• 关键词: Affect; Androgens; Apoptosis; Biochemical; Biology; Biomechanics; Cartilage; Cell Proliferation; Cervical; Cervix Uteri; Collagen; Congenital Abnormality; Disabled Persons; Elastin; Environment; Estrogens; Extracellular Matrix; Failure; Family; Goals; Growth; Growth Factor; Hormonal; Hormonal Change; Hormones; Integrins; Intervention; Learning Disabilities; Ligaments; Mechanical Stress; Mechanics; Mediating; Metabolism; Molecular; Morbidity - disease rate; Perinatal; Play; Pregnancy; Premature Birth; Premature Labor; Prevention; Process; Production; Progestins; Proteoglycan; Regulation; Regulatory Element; Resistance; Risk Factors; Role; Signal Pathway; Signal Transduction; Stimulus; Stromal Cells; System; Techniques; Tendon structure; Testing; Therapeutic Intervention; Tissues; Transforming Growth Factors; Weight-Bearing state; Wound Healing; base; cytokine; handicapping condition; in utero; mortality; premature; prevent; public health relevance; receptor; response; treatment site

DESCRIPTION (provided by applicant): Preterm birth remains the leading cause of perinatal morbidity and mortality after congenital birth defects affecting 1 of every 8 pregnancies. Cervical shortening has been recognized as a major risk factor for preterm birth. Shortening is likely to represent premature loss of normal mechanical function. The cervix has been recognized as a potential target for therapeutic intervention but little is known about its regulation. The principal function of the cervical extracellular matrix is to maintain the pregnancy in utero. The cervix undergoes biochemical changes during pregnancy that reduces its ability to resist mechanical forces that are thought to be mediated by both the hormonal environment and mechanical stress. The transforming growth factor 2 (TGF2) signaling pathway controls many tissue remodeling processes. Hormones and mechanical force have been shown to alter TGF2 signaling. The goal of this project is to determine the role of TGF2 in cervical matrix production during pregnancy. Three specific aims are identified: 1.) To determine the effects of TGF2 signaling on extracellular matrix metabolism within cervical stromal cells; 2.) To determine the effects of hormonal environment (Estrogens, Progestins, and Androgens) on TGF2 signaling leading to changes in cervical collagen metabolism; and 3.) To determine the role of mechanical strain on cervical extracellular matrix production. Molecular and biomechanical techniques will be used to evaluate the role of TGF2 signaling on extracellular matrix production. The effects of both hormonal environment and mechanical stress on TGF2 signaling will be investigated. By identifying key regulatory elements responsible for cervical extracellular matrix remodeling, interventions can be developed and tested to prevent cervical failure and preterm birth. PUBLIC HEALTH RELEVANCE: Preterm birth is a major contributor to learning disabilities and physical handicaps. The goal of this proposal is to identify new targets for therapeutic intervention that relate to cervical function and extracellular matrix remodeling. The cervical extracellular matrix is responsible for its primary mechanical function of maintaining the pregnancy to term.

描述（由申请人提供）：早产仍然是先天性出生缺陷后围产期发病率和死亡率的主要原因，影响每8例妊娠中的1例。宫颈缩短已被认为是早产的主要危险因素。缩短可能代表正常机械功能的过早丧失。子宫颈已被认为是一个潜在的治疗干预的目标，但很少有人知道它的调节。宫颈细胞外基质的主要功能是维持子宫内妊娠。子宫颈在怀孕期间经历生化变化，降低了其抵抗机械力的能力，这些机械力被认为是由激素环境和机械应力介导的。转化生长因子2（TGF 2）信号通路控制许多组织重塑过程。激素和机械力已经显示出改变TGF 2信号传导。该项目的目标是确定TGF-2在妊娠期间宫颈基质产生中的作用。确定了三个具体目标：（1）。确定TGF 2信号传导对宫颈基质细胞内细胞外基质代谢的影响; 2.）确定激素环境（雌激素、孕激素和雄激素）对导致宫颈胶原代谢变化的TGF 2信号传导的影响;和3.）确定机械应变对宫颈细胞外基质产生的作用。分子和生物力学技术将用于评估TGF 2信号传导对细胞外基质产生的作用。激素环境和机械应力对TGF 2信号传导的影响将被研究。通过识别负责宫颈细胞外基质重塑的关键调控元件，可以开发和测试干预措施以预防宫颈衰竭和早产。 公共卫生相关性：早产是导致学习障碍和身体残疾的主要因素。该提案的目标是确定与宫颈功能和细胞外基质重塑相关的治疗干预的新靶点。宫颈细胞外基质负责维持妊娠至足月的主要机械功能。