Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis
Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis
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DOI：
10.1183/09031936.00009407
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发表时间：
2007-08-01
影响因子：
24.3
通讯作者：
Breuer, R.
中科院分区：
文献类型：
--
作者：
Fridlender, Z. G.;Cohen, P. Y.;Breuer, R.
上皮细胞损伤和凋亡被认为是小鼠特发性肺纤维化和博莱霉素诱导的纤维化的早期特征。端粒酶是一种已知的肿瘤缓解因子。研究了端粒酶在体外博莱霉素诱导的小鼠肺上皮细胞（LEC）凋亡过程中的作用，以及在体内从博莱霉素处理的小鼠中分离的LEC中的作用。目前的作者用TRAPeze检测试剂盒评估了小鼠端粒酶逆转录酶（mTERT）mRNA水平的变化和端粒酶活性的变化，用TeloTTAGGG端粒长度试剂盒评估了端粒长度，用FACScan和4，6-diamino-2-phenylindole dihydrochloride染色，体外博莱霉素处理后24 h，mTERTmRNA显著升高，端粒酶活性短暂增加41%。在72小时，端粒酶活性下降到低于未处理细胞水平的26%。随着时间的推移，端粒酶活性的降低，或直接抑制，显着增加LEC凋亡。平均端粒长度没有变化。在体内实验中，博莱霉素处理的小鼠LECs在第7天和第14天的端粒酶活性均升高，端粒酶活性可能对博莱霉素诱导的肺上皮细胞凋亡具有保护作用。此外，稳定端粒酶活性可减少上皮细胞凋亡和由此产生的肺纤维化。
Epithelial cell injury and apoptosis are recognised as early features in idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase is a known apoptosis-alleviating factor. The role of telomerase was studied during bleomycin-induced lung epithelial cell (LEC) apoptosis in vitro in a mouse LEC line, and in vivo in LECs isolated from bleomycin-treated mice.The current authors evaluated changes in murine telomerase reverse transcriptase (mTERT) mRNA levels and changes in telomerase activity with the TRAPeze Detection Kit, telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with FACScan and 4,6-diamino-2-phenylindole dihydrochloride stain.There was a significant elevation in mTERT mRNA and a transient 41% increase in telomerase activity 24 h after in vitro bleomycin treatment. At 72 h, telomerase activity had fallen to 26% below levels in untreated cells. Reduction of telomerase activity over time, or by direct inhibition, significantly elevated LEC apoptosis. No change in average telomeric length was noted. In vivo, telomerase activity of LECs from bleomycin-treated mice increased at 7 and 14 days.In conclusion, telomerase activity may play a protective role against robust bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilising telomerase activity may decrease epithelial cell apoptosis and the resulting lung fibrosis.