Modulation of dead cell disposal and inflammatory signaling as novel approach to peritoneal membrane preservation in dialysis

调节死细胞处理和炎症信号作为透析中保存腹膜的新方法

• 批准号: 450775971
• 负责人: Professorin Dr. Sibylle von Vietinghoff
• 金额: --
• 依托单位: Medizinische Klinik und Poliklinik I - Allgemeine Innere Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/450775971?language=en
• 关键词: Modulation; dead; cell; disposal; inflammatory

Peritoneal dialysis (PD) for renal replacement therapy employs a biologic barrier, the peritoneal mesothelial wall, for clearance of uremic solutes and excess water and electrolytes. Chronic deterioration of peritoneal ultrafiltration capacity, a process that is promoted by hyperosmolar dialysis solutions and infectious peritonitides, limits its use. Peritoneal dialysis fluid induces excess cell death, but knowledge of the underlying pathways is very limited. We recently identified a new profibrotic interaction mechanism of macrophages with mesothelium and detected upregulation of a dead cell disposal (efferocytosis) molecule in protected mice. The present project Aim 1 is to delineate mechanisms of professional and nonprofessional phagocyte efferocytosis in PD. Aim 2 will study cell death, efferocytosis and underlying mechanisms in correlation to outcome in an established PD cohort and prospectively evaluate macrophage and mesothelial cell efferocytosis in incident and stable PD and in acute peritonitis. Aim 3 is to test its modulation as a novel therapeutic intervention strategy in PD associated fibrosis. Improvement of efferocytosis may serve as a new therapeutic angle for preservation of peritoneal function.

用于肾脏替代疗法的腹膜透析（PD）采用生物屏障，腹膜间皮壁，用于清除尿毒症溶质以及多余的水和电解质。腹膜超滤能力的慢性恶化，这是由高摩尔透析溶液和感染性腹膜促进的过程限制了其使用。腹膜透析液会诱导过多的细胞死亡，但是对基础途径的了解非常有限。我们最近确定了一种与间皮的巨噬细胞的新纤维化相互作用机制，并检测到受保护小鼠中死细胞处置（常见性胞吐）分子的上调。本项目的目的1是描述PD中专业和非专业吞噬细胞吞噬作用的机制。 AIM 2将研究既定的PD队列中与结果的相关性的细胞死亡，肿瘤病和潜在的机制，并前瞻性评估巨噬细胞和稳定的PD和急性腹膜炎中的巨噬细胞和间皮细胞效应。目标3是在PD相关纤维化中作为一种新型的治疗干预策略来测试其调制。肿瘤性肿瘤病的改善可能是保存腹膜功能的新治疗角度。