端粒功能障碍促进胆管细胞衰老和胆管纤维化在原发性硬化胆管炎
Nidhi Jalan-Sakrikar1,2,3, Abid Anwar1,2, Usman Yaqoob1,2
1Division of Gastroenterology and Hepatology.
JCI insight
|September 14, 2023
概括
初级硬化性胆道炎 (PSC) 涉及胆道纤维化和衰老,与端粒损伤有关. 恢复端粒酶逆转录酶 (TERT) 功能可能可以治疗这种端粒生物学障碍.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 细胞衰老和胆道纤维化是原发性硬化胆道炎 (PSC) 的关键特征.
- 端粒功能障碍,通过侵蚀或损伤,可以诱导细胞衰老.
研究的目的:
- 在PSC中调查端粒损伤和胆管纤维化之间的机械联系.
- 探索端粒酶逆转录酶 (TERT) 在PSC病变发生中的作用.
主要方法:
- 从PSC患者和小鼠模型中分析胆管,以测量端粒磨损和TERT表达.
- 在体外研究中,使用胆细胞衰老模型来评估与端粒相关的焦点 (TAF) 和TERT水平.
- 对TERT促进体的表观遗传学分析以及涉及TERT删除和小鼠的雄激素治疗的功能性研究.
主要成果:
- 在PSC患者和小鼠模型中表现出端粒磨损和胆管中TERT表达的减少.
- 胆细胞衰老模型显示TAF增加,TERT减少,并在TERT调节后恢复衰老.
- 在小鼠中,TERT缺乏症加剧了纤维化,而雄激素治疗在PSC模型中改善了肝纤维化和功能.
结论:
- 端粒功能障碍在PSC相关的细胞衰老和胆管纤维化中起着机械作用.
- 原发性硬化性胆道炎可能部分是端粒生物学疾病.
- TERT代表了PSC的潜在治疗目标.
相关概念视频
Chronic Pancreatitis I: Introduction
112
The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
112
Replicative Cell Senescence
3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
Chronic Bowel Disorders: Introduction
478
Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
478


