Telomere-mediated lung disease.
Telomere-mediated lung disease.
复制标题
端粒介导的肺部疾病。
DOI：
10.1152/physrev.00046.2021
复制
发表时间：
2022-10-01
影响因子：
33.6
通讯作者：
Armanios, Mary
中科院分区：
文献类型：
--
作者：
Alder, Jonathan K.;Armanios, Mary
实质肺疾病是美国第四大死因；在最主要的原因中，它还在继续上升。从历史上看，端粒和端粒酶与衰老和癌症相关的细胞过程有关，但令人惊讶的是，近十年来，基因发现将人类端粒和端粒酶功能障碍的最明显表现与肺部疾病的病因联系起来：特发性肺纤维化（IPF）和肺气肿。短端粒缺陷在IPF患者中普遍存在，而人类IPF是与端粒维持中的种系缺陷最密切相关的表型。三分之一的肺纤维化家庭携带端粒酶或其他端粒维持基因的种系突变，一半的明显散发性IPF患者端粒长度短。除了解释遗传易感性之外，短端粒长度揭示了临床相关的综合征性肺外疾病，包括t细胞免疫缺陷和髓系恶性肿瘤的倾向。认识到这部分患者具有统一的分子缺陷，提供了一种精准医学范式，其中端粒介导的肺部疾病诊断比组织病理学或多学科评估提供了更多的预后价值。在这里，我们批判性地评估这一进展，强调遗传发现如何提出了与年龄相关的肺部疾病的新发病模式，将端粒异常与肺泡干衰老、重塑和气体交换缺陷联系起来。
Parenchymal lung disease is the fourth leading cause of death in the United States; among the top causes, it continues on the rise. Telomeres and telomerase have historically been linked to cellular processes related to aging and cancer, but surprisingly, in the recent decade genetic discoveries have linked the most apparent manifestations of telomere and telomerase dysfunction in humans to the etiology of lung disease: both idiopathic pulmonary fibrosis (IPF) and emphysema. The short telomere defect is pervasive in a subset of IPF patients, and human IPF is the phenotype most intimately tied to germline defects in telomere maintenance. One-third of families with pulmonary fibrosis carry germline mutations in telomerase or other telomere maintenance genes, and one-half of patients with apparently sporadic IPF have short telomere length. Beyond explaining genetic susceptibility, short telomere length uncovers clinically relevant syndromic extrapulmonary disease, including a T-cell immunodeficiency and a propensity to myeloid malignancies. Recognition of this subset of patients who share a unifying molecular defect has provided a precision medicine paradigm wherein the telomere-mediated lung disease diagnosis provides more prognostic value than histopathology or multidisciplinary evaluation. Here, we critically evaluate this progress, emphasizing how the genetic findings put forth a new pathogenesis paradigm of age-related lung disease that links telomere abnormalities to alveolar stem senescence, remodeling, and defective gas exchange.
登录
查看更多内容
影响因子：
4.5
作者：
Aubert G;Baerlocher GM;Vulto I;Poon SS;Lansdorp PM
通讯作者：
Lansdorp PM
影响因子：
14.9
作者：
Cawthon RM
通讯作者：
Cawthon RM
DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
Alder, Jonathan K.;Parry, Erin M.;Yegnasubramanian, Srinivasan;Wagner, Christa L.;Lieblich, Lawrence M.;Auerbach, Robert;Auerbach, Arleen D.;Wheelan, Sarah J.;Armanios, Mary
通讯作者：
Armanios, Mary
影响因子：
1.7
作者：
Degryse AL;Xu XC;Newman JL;Mitchell DB;Tanjore H;Polosukhin VV;Jones BR;McMahon FB;Gleaves LA;Phillips JA 3rd;Cogan JD;Blackwell TS;Lawson WE
通讯作者：
Lawson WE