The Enteric Glia as a Possible Target for Symptom Relief in Endometriosis

肠胶质细胞作为缓解子宫内膜异位症症状的可能目标

• 批准号: 10625609
• 负责人: Caroline B Appleyard
• 金额: $ 15.68万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625609
• 关键词: Adhesions; Affect; Age; Agonist; Anatomy; Animal Model; Animals; Anti-Inflammatory Agents; Area; Astrocytes; Behavioral; Cells; Chronic; Clinical Management; Colitis; Colon; Complex; Data; Development; Disease; Electrocardiogram; Endometrial; Enteral; Enteric Nervous System; Environment; Exercise; Exposure to; Female Genital Diseases; Fibrosis; Functional disorder; Genetic Transcription; Gland; Glial Fibrillary Acidic Protein; Goals; Gynecologic; Illness Days; Immune; Inflammation; Inflammatory; Inflammatory Response; Institution; Insurance; Interdisciplinary Study; Intervention; Intestinal Diseases; Intestines; Investigation; Irritable Bowel Syndrome; Lesion; Life; Ligands; Localized Lesion; Mediating; Medical Care Costs; NF-kappa B; Neuroglia; Nutritional; Outcome; Ovarian Cysts; Oxidative Stress; PPAR gamma; Pain; Parasympathetic Nervous System; Pathway interactions; Patients; Pelvis; Peritoneal; Personal Satisfaction; Phenotype; Process; Productivity; Program Sustainability; Protocols documentation; Research; Research Project Grants; Role; S-Nitrosoglutathione; Science; Severities; Source; Spinal; Stains; Stress; Symptoms; Translating; Translational Research; Uterine cavity; Vertebral column; Vesicle; Woman; Women' s Health; Work; behavioral response; chronic pelvic pain; cytokine; daily functioning; design; economic cost; economic impact; endometriosis; environmental enrichment for laboratory animals; gastrointestinal symptom; glial cell-line derived neurotrophic factor; graduate student; immune activation; implantation; improved; inflammatory modulation; inflammatory pain; interest; intervention effect; nerve supply; neurotrophic factor; new therapeutic target; novel; novel therapeutic intervention; programs; protein expression; reduce symptoms; reproductive; stress reduction; subfertility; training opportunity; undergraduate student

Endometriosis, a chronic painful gynecological disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity, is characterized by peritoneal inflammation, fibrosis, adhesions, and ovarian cysts. Women with endometriosis often present gastrointestinal symptoms independent of lesion localization. Enteric glial cells (EGCs) are astrocyte-like cells that are vital to the enteric nervous system and play a role in gut diseases. The role of intestinal glia in endometriosis is unknown; however, a bidirectional relationship between the EGC and immune cells in the modulation of the inflammatory response and pain sensitization is postulated. Enteric glia can produce an endogenous ligand for peroxisome proliferator activated receptor gamma (PPAR) with anti-inflammatory activity. PPAR agonists in endometriosis animal models reduce vesicle size. The study team’s previous work has demonstrated that exercise can increase expression and activity of PPAR, while reducing vesicle size and development. The main objective is to examine the role of EGC in the pathophysiology of endometriosis with the long-term goal of finding new therapeutic targets. The study team hypothesizes that endometriosis-induced immune activation is regulated by ECG which promotes and maintains chronic inflammation, and that this can be reversed by non-pharmacological complementary interventions. Aim 1 will determine how endometriosis impacts the enteric glia and how this correlates with pain. Aim 2 will elucidate whether the beneficial effects of interventions, such as exercise and environmental enrichment, are mediated by PPAR. Rationale: complementary interventions will impact the enteric glia via parasympathetic activation, shifting it from the endometriosis-induced, pro-inflammatory phenotype to an anti-inflammatory one, decreasing proinflammatory cytokine release and oxidative stress. Successful outcomes could explain chronic pelvic inflammation and gastrointestinal symptoms and provide a novel target. This study will contribute to the goals of the SuRE program by sustaining the research excellence of the PI and strengthening the institutional research environment. This study will provide graduate and undergraduate students at various levels with opportunities in multidisciplinary research areas to encourage their continued involvement in biomedical sciences research and stimulate their interest in novel integrative interventions.

子宫内膜异位症，一种慢性疼痛妇科疾病，定义为子宫内膜腺的存在 子宫内膜腔外的基质的特征是腹膜注射，纤维化，粘合剂， 和卵巢囊肿。子宫内膜异位症的妇女经常出现胃肠道症状独立于 病变定位。肠神经胶质细胞（EGC）是星形胶质细胞样细胞，对肠神经至关重要 系统并在肠道疾病中发挥作用。肠道神经胶质在子宫内膜异位中的作用尚不清楚。但是， EGC和免疫细胞之间的双向关系调节 响应和疼痛敏感性已发布。肠神经胶质可以产生内源配体 过氧化物组增殖物激活受体伽马（PPAR）具有抗炎活性。 ppar 子宫内膜异位动物模型中的激动剂减少了蔬菜的大小。学习团队以前的工作 证明运动可以增加PPAR的表达和活性，同时降低蔬菜尺寸 和发展。主要目的是检查EGC在病理生理中的作用 子宫内膜异位症具有寻找新的治疗靶标的长期目标。研究团队假设 子宫内膜异位症诱导的免疫激活受ECG调节，ECG促进和维持慢性 炎症，这可以通过非药理完整的干预措施来逆转。目标1 将确定子宫内膜异位症如何影响肠神经胶质细胞，以及它与疼痛的相关性。 AIM 2意志 阐明干预措施的有益影响，例如运动和环境富集， 由PPAR介导。理由：完整的干预措施将通过 副交感神经激活将其从子宫内膜异位症诱导的促炎表型转移到 抗炎的一种，减少促炎性细胞因子释放和氧化应激。 成功的结果可以解释慢性骨盆注射和胃肠道症状以及 提供一个新颖的目标。这项研究将通过维持确保计划的目标做出贡献 PI的卓越研究并增强了机构研究环境。这项研究会 为研究生和本科生提供各个级别的多学科机会 研究领域，以鼓励他们继续参与生物医学科学研究并刺激 他们对新型综合干预措施的兴趣。