Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery
Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery
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DOI：
10.1126/science.287.5456.1253
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发表时间：
2000-02-18
期刊：
影响因子：
56.9
通讯作者：
DePinho, RA
中科院分区：
文献类型：
--
作者：
Rudolph, KL;Chang, S;DePinho, RA
端粒加速丢失被认为是导致高细胞更新的慢性疾病如肝硬化的终末期器官衰竭的一个因素。为了直接验证这一假设，端粒酶缺陷小鼠，无效的基本端粒酶RNA（mTR）基因，进行遗传，手术和化学消融的肝脏。端粒功能障碍与肝再生缺陷有关，并加速了慢性肝损伤后肝硬化的发展。将mTR腺病毒递送到具有短的功能失调的端粒的mTR（-/-）小鼠的肝脏中恢复了端粒酶活性和端粒功能，减轻了肝硬化病理，并改善了肝功能。这些研究表明，端粒功能障碍有助于慢性疾病的持续细胞损失替代，并鼓励评估“端粒酶治疗”这类疾病。
Accelerated telomere loss has been proposed to be a factor Leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR(-/-) mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of "telomerase therapy" for such diseases.