课题基金基金详情
脂肪细胞源exosomes介导血管新生在2型糖尿病肾病中的作用
结题报告
批准号:
82000681
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王峰
依托单位:
学科分类:
继发性肾脏疾病
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王峰
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中文摘要
糖尿病肾病是终末期肾病的首要原因,病理性血管新生是糖尿病肾病发病机制中的早期关键事件,而炎症是血管新生重要驱动因素,脂肪组织是机体炎症反应最早、最主要的发源地。但是脂肪组织能否通过释放exosomes架起脂肪组织炎症和病理性血管新生之间的桥梁,促进糖尿病肾病进展尚不清楚。我们前期研究表明脂肪细胞来源的exosomes(ADEs)携带促血管新生Sonic hedgehog蛋白。因此,我们提出脂肪组织通过ADEs及其携带的Sonic hedgehog蛋白架起了糖尿病状态下脂肪组织炎症和病理性血管新生之间桥梁的研究计划。本课题拟在细胞、动物2个层面,利用透射电镜、流式细胞术、纳米颗粒跟踪分析技、基因工程、分子生物学等技术,深入探讨ADEs通过Sonic hedgehog信号通路促进糖尿病肾病血管新生,进而影响糖尿病肾病进展。研究结果将为糖尿病肾病的早期防治提供新的靶点。
英文摘要
Diabetic nephropathy is the leading cause of end-stage renal disease. Abnormal angiogenesis has a pivotal role in the progression of diabetic nephropathy, and inflammation is an important driving factor for angiogenesis. Adipose tissue is the earliest and most important source of inflammation in the body. However, it still remains unclear whether exosomes released from adipose tissue can bridge the gap between adipose tissue inflammation and pathological angiogenesis promoting the progression of diabetic nephropathy. Our previous studies have shown that adipose-derived exosomes (ADEs) carry the angiogenic Sonic hedgehog protein. Therefore, we hypothesize that adipose tissue organizes a bridge between adipose tissue inflammation and pathological angiogenesis in diabetes through ADEs harboring Sonic hedgehog protein. At levels of cell and animal, We intended to conduct systematic and in-depth exploration of the mechanism by which explore Sonic hedgehog signaling pathway mediated by ADEs promote angiogenesis and further effect the progression of diabetic nephropathy, taking advantage of the various techniques such as transmission electron microscope, flow cytometry, nanoparticle tracking analysis, genetic engineering and molecular biological techniques, etc. The results of the study will provide new targets for the early prevention and treatment of diabetic nephropathy.
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