Telomerase regulation of myofibroblast differentiation
Telomerase regulation of myofibroblast differentiation
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DOI：
10.1165/rcmb.2005-0252oc
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发表时间：
2006-05-01
影响因子：
6.4
通讯作者：
Phan, SH
中科院分区：
文献类型：
--
作者：
Liu, T;Hu, B;Phan, SH
在肿瘤细胞中广泛表达的端粒酶活性在肺增殖性成纤维细胞中被诱导。与肌成纤维细胞相比，它在成纤维细胞中优先表达。目前尚不清楚端粒酶表达的调节是否与成纤维细胞分化为肌成纤维细胞的过程有关。这项研究的目的是阐明端粒酶表达和肌成纤维细胞分化之间的潜在联系。端粒酶抑制剂3‘叠氮-2’，3‘-二脱氧胸苷或端粒酶RNA组分的反义寡核苷酸用于抑制诱导的成纤维细胞端粒酶活性。结果表明，抑制诱导的端粒酶增加了α-平滑肌肌动蛋白的表达，这是肌成纤维细胞分化的指标。相反，碱性成纤维细胞生长因子诱导的端粒酶抑制α-平滑肌肌动蛋白的表达。这些发现表明端粒酶活性的丧失与肌成纤维细胞的分化密切相关，并可能是肌成纤维细胞分化的触发因素。相反，端粒酶的表达抑制了肌成纤维细胞的分化。
Telomerase activity, which has wide expression in cancerous cells, is induced in lung proliferating fibroblasts. It is preferentially expressed in fibroblasts versus myofibroblasts. It is unknown whether regulation of telomerase expression is related to the process of fibroblast differentiation into myofibroblasts. The objective of this study was to clarify such a potential link between telomerase expression and myofibroblast differentiation. Telomerase inhibitor, 3'azido-2',3'-dideoxythymidine, or antisense oligonucleotide to the telomerase RNA component was used to inhibit the induced fibroblast telomerase activity. The results showed that inhibition of induced telomerase increased alpha-smooth muscle actin expression, an indicator of myofibroblast differentiation. In contrast, induction of telomerase by basic fibroblast growth factor inhibited a-smooth muscle actin expression. These findings suggest that the loss of telomerase activity is closely associated with myofibroblast differentiation and possibly functions as a trigger for myofibroblast differentiation. Conversely, expression of telomerase suppresses myofibroblast differentiation.