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，定义为子宫内膜腺的存在