依赖于氧化的骨髓硬化促进了糖尿病中性粒细胞的激活
Mahesh Agarwal1,2, Sathishkumar Chandrakumar2, Vihar Trada3
1Department of Ophthalmology, University of California, Los Angeles, CA, USA 90095.
bioRxiv : the preprint server for biology
|September 15, 2025
概括
糖尿病导致骨髓硬,机械激活中性粒细胞. 抑制lysyl氧化酶 (LOX) 逆转了这种情况,为糖尿病血管并发症提供了一个新的治疗点.
科学领域:
- 生物医学工程 生物医学工程
- 血管生物学 血管生物学
- 糖尿病学 糖尿病学
背景情况:
- 持续的中性粒细胞激活是糖尿病血管并发症的关键因素.
- 以前的研究集中在中性粒细胞激活的分子和生化触发剂上.
研究的目的:
- 研究骨髓 (BM) 机械特性在糖尿病中中性粒细胞激活中的作用.
- 确定 lysyl氧化酶 (LOX) 作为糖尿病诱导的肌肉硬化和中性粒细胞激活的关键媒介.
主要方法:
- 使用糖尿病小鼠模型和β-aminopropionitrile (BAPN),一种LOX抑制剂.
- 评估了BM矩阵刚度,中性粒细胞激活标记 (超氧化物生成,gp91phox) 和对视网膜内皮细胞的细胞毒性.
- 采用可调节的水凝来模仿BM硬性和研究中性粒细胞机械传导.
主要成果:
- 糖尿病通过原和LOX过度表达增加了BM度,导致机械中性粒细胞激活.
- BAPN治疗使BM硬度正常化,并抑制了中性粒细胞激活和细胞毒性.
- 发现矩阵局部化和可溶性LOX都能协同激活BM内的中性粒细胞.
结论:
- 骨髓物理环境中的LOX-依赖性变化代表了糖尿病血管并发症的新机制.
- 针对LOX和骨髓的机械特性,为涉及中性粒细胞激活的糖尿病并发症提供了潜在的治疗策略.
更多相关视频
相关概念视频
Pathophysiology of Diabetes
3.2K
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
3.2K
Psychoneuroimmunology: Diabetes and Cancer
461
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
461


