Regulation of telomerase activity in rat lung fibroblasts
Regulation of telomerase activity in rat lung fibroblasts
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DOI：
10.1165/ajrcmb.26.5.4668
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发表时间：
2002-05-01
影响因子：
6.4
通讯作者：
Phan, SH
中科院分区：
文献类型：
--
作者：
Liu, TJ;Nozaki, Y;Phan, SH
博莱霉素损伤肺成纤维细胞在活动性纤维化期短暂表达端粒酶活性，但诱导端粒酶活性的信号(S)尚不清楚。本研究的目的是确定在肺纤维化过程中能够调节大鼠肺成纤维细胞端粒酶活性诱导的潜在介质。分离对照组(NRF)和博莱霉素组(BRF)大鼠肺成纤维细胞，分别用碱性成纤维细胞生长因子(BFGF)和白介素4(IL-4)处理。分别用逆转录聚合酶链式反应和Western印迹法检测细胞端粒酶活性和端粒酶逆转录酶(TERT)mRNA和蛋白的表达。结果表明，碱性成纤维细胞生长因子可诱导NRF端粒酶活性，进一步刺激BRF的端粒酶活性。碱性成纤维细胞生长因子的作用伴随着TERT蛋白表达的增加和TERT mRNA的快速但短暂的增加。相反，IL-4抑制BRF中诱导的端粒酶活性，同时伴随着α-平滑肌肌动蛋白表达的增加，这是肌成纤维细胞分化的指标。提示碱性成纤维细胞生长因子可诱导大鼠肺成纤维细胞端粒酶的表达，而IL-4可抑制端粒酶的表达，从而促进肌成纤维细胞分化。后者与成纤维细胞中端粒酶活性相对于肌成纤维细胞的优先表达相一致。
Fibroblasts from bleomycin-injured lungs express telomerase activity transiently during the period of active fibrosis, but the signal(s) responsible for its induction is (are) unknown. The objective of this study was to identify potential mediators capable of regulating telomerase activity induction in rat lung fibroblasts during pulmonary fibrosis. Lung fibroblasts from control (NRF) and bleomycin-treated (BRF) rats were isolated and treated in vitro with either basic fibroblast growth factor (bFGF) or interleukin-4 (IL-4). At selected time points after treatment, the cells were analyzed for telomerase activity, as well as telomerase reverse transcriptase (TERT) mRNA and protein by reverse transcriptase/polymerase chain reaction and Western blot, respectively. The results showed that bFGF could induce telomerase activity in NRF and stimulate further the induced activity in BRF. The bFGF effect was accompanied by increased TERT protein expression and a rapid but transient increase in TERT mRNA. In contrast, IL-4 inhibited the induced telomerase activity in BRF, which was accompanied by increased a-smooth muscle actin expression, an indicator of myofibroblast differentiation. These findings suggest that telomerase expression could be induced in rat lung fibroblasts by bFGF, but suppressed by IL-4, which promoted myofibroblast differentiation. The latter is consistent with the preferential expression of telomerase activity in fibroblasts relative to myofibroblasts.