一氧化碳通过调节p53/PAI-1通路来减轻细胞衰老介导的肺纤维化
Qianqian Wang1, Aohan Li2, Qian Li2
1Engineering Technology Research Center for the Utilization of Functional Components of Organic Natural Products, Dalian University, Dalian, 116622, Liaoning, China; Chronic Disease Research Center, Medical College, Dalian University, Dalian, 116622, Liaoning, China.
European journal of pharmacology
|July 28, 2024
概括
一氧化碳释放分子2 (CORM2) 通过减少细胞衰老和DNA损伤来预防肺纤维化. 这为异形性肺纤维化 (IPF) 治疗提供了一个有希望的策略.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 异形性肺纤维化 (IPF) 是一种渐进的肺病,通常需要移植.
- 第二类膜上皮细胞 (AECII) 的加速衰老及其与衰老相关的分泌表型 (SASP) 驱动纤维化.
- 低剂量的一氧化碳 (CO) 具有抗炎,抗氧化和抗衰老的特性.
研究的目的:
- 在白血素诱导的肺纤维化模型中研究CO释放分子2 (CORM2) 的预防潜力.
- 阐明CORM2影响细胞衰老和纤维化进展的机制.
主要方法:
- 在C57BL/6J小鼠中诱导了肺纤维化.
- 通过组织学染色,肺功能测试和分子分析 (qRT-PCR,西部斑,ELISA) 来评估CORM2治疗效果.
- 在体内和体外使用免疫光和SA-β-gal染色来评估DNA损伤,细胞衰老和SASP.
主要成果:
- 科尔米2治疗改善了肺功能,并减少了纤维化标志物 (TGF-β,α-SMA,原I/III).
- CORM2抑制了DNA损伤反应 (γ-H2AX,p53,p21) 和PAI-1的表达.
- CORM2抑制了AECII衰老,并延迟了上皮层-介质细胞过渡 (EMT).
结论:
- 在肺纤维化中,CORM2证明了对DNA损伤引起的细胞衰老的预防作用.
- 调节p53/PAI-1信号通路是CORM2作用的一个关键机制.
- 通过准细胞衰老,CORM2为IPF提供了一个有前途的治疗策略.
相关概念视频
Chronic Obstructive Pulmonary Disease-II: Pathophysiology
2.7K
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
2.7K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Mitochondria
11.8K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
11.8K
COPD: Pathogenesis and Clinical Features
251
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...
251
Negative Regulator Molecules
35.3K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.3K
Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K


