Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a
Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a
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DOI：
10.1182/blood-2011-12-400002
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发表时间：
2012-06-14
期刊：
影响因子：
20.3
通讯作者：
Dorshkind, Kenneth
中科院分区：
文献类型：
--
作者：
Berent-Maoz, Beata;Montecino-Rodriguez, Encarnacion;Dorshkind, Kenneth
胸腺退化导致幼稚T细胞的产生减少，这反过来被认为是导致老年人免疫力下降的原因之一。早期T细胞前体细胞(ETPs)是胸腺内最不成熟的T细胞前体细胞，从消退的胸腺中获得，其增殖能力减弱，凋亡率增加，其数量显著减少。在目前的研究中，我们表明这些年龄诱导的改变部分是由于在ETP中Ink4a肿瘤抑制基因的表达增加。我们还表明，抑制Ink4a在老年ETP中会导致其部分恢复活力，这可以通过体内注射成纤维细胞生长因子7来实现。这些结果确定了胸腺细胞前体细胞衰老的遗传学基础，并表明衰老相关基因Ink4a可以在ETP中被药物抑制，以部分逆转衰老的影响。(血。2012年；119(24)：5715-5721)
Involution of the thymus results in reduced production of naive T cells, and this in turn is thought to contribute to impaired immunity in the elderly. Early T-cell progenitors (ETPs), the most immature intrathymic T-cell precursors, harvested from the involuted thymus exhibit a diminished proliferative potential and increased rate of apoptosis and as a result their number is significantly reduced. In the present study, we show that these age-induced alterations result in part from increased expression of the Ink4a tumor-suppressor gene in ETPs. We also show that repression of Ink4a in aged ETPs results in their partial rejuvenation and that this can be accomplished by in vivo fibroblast growth factor 7 administration. These results define a genetic basis for thymocyte progenitor aging and demonstrate that the senescence-associated gene Ink4a can be pharmacologically repressed in ETPs to partially reverse the effects of aging. (Blood. 2012; 119(24):5715-5721)