DEC1参与昼夜节律扰乱-恶化的肺纤维化
Shuai-Jun Chen1,2, Fan Yu1,3, Xiao Feng2
1Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, 430022, Wuhan, China.
Cell communication and signaling : CCS
|April 26, 2024
概括
循环时钟蛋白DEC1通过通过p21促进膜上皮细胞II型 (AT2) 衰老,加剧肺纤维化. 抑制DEC1减轻纤维化和AT2细胞衰老,揭示了肺部疾病的关键机制.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 时间生物学 时间生物学
背景情况:
- 膜上皮类型II细胞 (AT2) 和它们的衰老在肺损伤和纤维化中至关重要.
- 细胞昼夜节律与衰老有关,其中DEC1是一个关键的昼夜钟基因.
- DEC1在AT2细胞衰老和肺纤维化中的特定作用尚不清楚.
研究的目的:
- 研究DEC1在AT2细胞衰老和肺纤维化中的作用.
- 阐明DEC1影响这些过程的潜在机制.
主要方法:
- 在小鼠中使用昼夜干扰模型 (光干预).
- 分析了异常性肺纤维化 (IPF) 患者的肺组织中的DEC1水平,以及白色素诱导的纤维化小鼠肺部.
- 对用白素和TGF-β1.1治疗的AT2细胞进行了体外研究.
- 在体外和体内研究了DEC1抑制的效果.
- 评估细胞衰老和p21表达与DEC1和昼夜节律相关.
主要成果:
- 循环节障碍使小鼠的肺纤维化恶化.
- 在IPF患者肺部和纤维化小鼠肺部,DEC1水平升高.
- 白素和TGF-β1在AT2细胞中增加了DEC1,原-I和纤维素.
- DEC1抑制减少了纤维变化,并防止了白血素诱导的AT2细胞衰老.
- 布莱米辛扰乱了昼夜节律,增加了DEC1,增加了p21表达,并调解了AT2衰老和纤维化.
结论:
- 昼夜时钟蛋白DEC1调解了肺纤维化.
- DEC1通过p21和AT2细胞衰老促进肺纤维化.
- 准DEC1可能为肺纤维化提供治疗策略.
相关概念视频
02:19Circadian Rhythms and Gene Regulation
4.0K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.0K
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
2.8K
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
2.8K
01:20Chronic Obstructive Pulmonary Disease-I: Introduction
2.8K
Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting respiratory condition requiring continuous attention and care. It is a progressive lung disease that leads to breathing challenges due to airflow obstruction. It manifests as persistent respiratory symptoms and restricted airflow resulting from abnormalities in the airways and alveoli, usually due to long-term exposure to harmful particles or gases. COPD mainly consists of two primary conditions: emphysema and chronic bronchitis.
2.8K
01:20COPD: Pathogenesis and Clinical Features
265
Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
265
01:23Cystic Fibrosis: Pathogenesis
224
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,...
224