高血糖症对WT和CF 16HBE细胞呼吸道上皮质屏障功能的影响
Analia J Vazquez Cegla1,2,3, Kymry T Jones1,2,3, Guiying Cui1,2
1Division of Pulmonology, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Scientific reports
|October 24, 2024
概括
囊性纤维化相关糖尿病 (CFRD) 恶化了呼吸道屏障功能,特别是在高血糖的情况下. 在CF细胞中,克劳丁-4 (CLDN4) 紧结蛋白错位导致这种缺陷,但调节器可以恢复屏障的完整性.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 囊性纤维化相关糖尿病 (CFRD) 是囊性纤维化 (CF) 患者的主要并发症.
- CFRD与加速的肺功能下降有关.
- 空气道上皮质屏障功能障碍可能会导致CFRD的负面肺结局.
研究的目的:
- 为了研究高血糖症对气道上皮质屏障功能的影响,CF.
- 为了确定关键的分子参与者参与阻碍功能障碍在CF的高血糖条件下.
主要方法:
- 利用16HBE细胞 (人类支气管上皮细胞系) 来建模CF和健康对照.
- 通过染料流量测试评估了对细胞的通透性.
- 通过基因表达和共聚焦显微镜检查了Claudin-4 (CLDN4) 的表达和定位.
- 进行大量RNA测序以确定差异性基因表达模式.
- 研究了CFTR调节器疗法 (ETI) 的影响.
主要成果:
- 过高血糖症增加了CF细胞中的等细胞染料流量,表明屏障受损.
- 克劳丁-4 (CLDN4) 显示 CF 细胞紧密结节的局部受损,在高血糖下恶化.
- 有效调节器疗法 (ETI) 恢复了CF细胞中的CLDN4局部化和屏障功能.
- 大量RNA测序揭示了CF与WT细胞在不同的葡萄糖条件下不同的转录特征,确定了PTPRG作为潜在的目标.
结论:
- 空气道上皮质屏障功能障碍在CF中被高血糖症加剧,导致肺部问题.
- 在高血糖条件下,克劳丁-4 (CLDN4) 失调是CF气道屏障受损的关键因素.
- CFTR调节器疗法在恢复气道屏障功能方面表现有希望,并为CFRD提供潜在的治疗途径.
更多相关视频
06:26Analyzing the Permeability of the Blood-Brain Barrier by Microbial Traversal through Microvascular Endothelial Cells
Published on: February 14, 2020
15.4K
10:26P. aeruginosa Infected 3D Co-Culture of Bronchial Epithelial Cells and Macrophages at Air-Liquid Interface for Preclinical Evaluation of Anti-Infectives
Published on: June 15, 2020
10.7K
相关概念视频
01:23Cystic Fibrosis: Pathogenesis
192
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
192
01:20Pathophysiology of Diabetes
874
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,...
874
01:19Overview of Carbohydrate Metabolism
762
Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
762