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，一种慢性疼痛的妇科疾病，定义为子宫内膜腺体的存在 和子宫内膜腔外的间质，其特征在于腹膜炎症、纤维化、粘连， 卵巢囊肿患有子宫内膜异位症的女性通常会出现胃肠道症状， 病灶定位肠神经胶质细胞（EGCs）是一种星形胶质细胞样细胞，在肠神经系统中起重要作用。 系统，并在肠道疾病中发挥作用。肠神经胶质细胞在子宫内膜异位症中的作用尚不清楚，然而， EGC和免疫细胞在炎症调节中的双向关系 反应和疼痛敏感性的假设。肠神经胶质细胞可以产生内源性配体， 具有抗炎活性的过氧化物酶体增殖物激活受体γ（PPAR γ）。PPAR γ 子宫内膜异位症动物模型中的激动剂减小囊泡大小。研究小组以前的工作 研究表明，运动可以增加PPAR γ的表达和活性，同时减少囊泡大小， 发展先行者的要求主要目的是研究EGC在胃肠道疾病的病理生理学中的作用。 子宫内膜异位症的长期目标是寻找新的治疗靶点。研究小组假设， 糖尿病诱导的免疫激活受ECG调节，其促进和维持慢性炎症。 炎症，并且这可以通过非药物补充干预来逆转。要求1 将确定子宫内膜异位症如何影响肠神经胶质细胞以及这与疼痛的关系。目标2将 阐明干预措施的有益效果，如运动和环境富集， 由过氧化物酶体增殖物激活受体介导。理由：补充干预将通过以下方式影响肠神经胶质细胞： 副交感神经激活，将其从糖尿病诱导的促炎表型转变为 抗炎作用，减少促炎细胞因子释放和氧化应激。 成功的结果可以解释慢性盆腔炎和胃肠道症状， 提供了一个新的目标。本研究将通过维持 研究卓越的PI和加强机构的研究环境。本研究将 为各级研究生和本科生提供多学科的机会 研究领域，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的兴趣。