Telomerase deficiency does not alter bleomycin-induced fibrosis in mice.
Telomerase deficiency does not alter bleomycin-induced fibrosis in mice.
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DOI：
10.3109/01902148.2012.658148
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发表时间：
2012-04
影响因子：
1.7
通讯作者：
Lawson WE
中科院分区：
文献类型：
--
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
特发性肺纤维化（IPF）的特征是肺间质浸润、呼吸困难和进行性呼吸衰竭。家族性间质性肺炎（FIP）与端粒酶突变相关的报道表明，端粒酶活性和端粒长度的维持在疾病的发病机制中很重要。为了研究端粒酶在肺纤维化重塑中的作用，将博莱霉素注射到端粒酶逆转录酶（TERT）或端粒酶RNA组分（TERC）缺陷的小鼠和野生型对照组中。将TERT缺陷型和TERC缺陷型小鼠分别与F6和F4代杂交，当它们出现皮肤表现和不育时。使用半定量量表对纤维化进行评分，并使用羟脯氨酸微孔板测定法测量肺总胶原。在外周血白细胞和分离的II型肺泡上皮细胞（AEC）中测量端粒长度。使用基于真实的时间PCR的系统测量II型AEC中的端粒酶活性。在博来霉素后，与对照组相比，TERT缺陷型和TERC缺陷型小鼠产生了等同的炎症反应和相似的肺纤维化（通过肺切片和总肺胶原含量的评分），这种模式在早期世代（F1）和后期世代（F6 TERT和F4 TERC）中均可见。与对照组相比，F6 TERT和F4 TERC小鼠外周血白细胞和分离的II型AEC中的端粒长度减少。小鼠模型中的端粒酶缺陷导致端粒缩短，但不倾向于增强博莱霉素诱导的肺纤维化。在存在端粒酶缺陷的情况下，其他遗传或环境因素可能是纤维化发展所必需的。
Idiopathic pulmonary fibrosis (IPF) is characterized by interstitial lung infiltrates, dyspnea, and progressive respiratory failure. Reports linking telomerase mutations to familial interstitial pneumonia (FIP) suggest that telomerase activity and telomere length maintenance are important in disease pathogenesis. To investigate the role of telomerase in lung fibrotic remodeling, intratracheal bleomycin was administered to mice deficient in telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) and wild type controls. TERT deficient and TERC deficient mice were interbred to the F6 and F4 generation, respectively, when they developed skin manifestations and infertility. Fibrosis was scored using a semiquantitative scale and total lung collagen was measured using a hydroxyproline microplate assay. Telomere lengths were measured in peripheral blood leukocytes and isolated type II alveolar epithelial cells (AECs). Telomerase activity in type II AECs was measured using a real time PCR based system. Following bleomycin, TERT deficient and TERC deficient mice developed an equivalent inflammatory response and similar lung fibrosis (by scoring of lung sections and total lung collagen content) compared to controls, a pattern seen in both early generation (F1) and later generations (F6 TERT and F4 TERC). Telomere lengths were reduced in peripheral blood leukocytes and isolated type II AECs from F6 TERT and F4 TERC mice compared to controls. Telomerase deficiency in a murine model leads to telomere shortening, but does not predispose to enhanced bleomycin induced lung fibrosis. Additional genetic or environmental factors may be necessary for development of fibrosis in the presence of telomerase deficiency.
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DOI：
10.1513/pats.200512-137tk
发表时间：
2006-06-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
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作者：
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通讯作者：
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影响因子：
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