MicroRNA-570 is a novel regulator of cellular senescence and inflammaging.
MicroRNA-570 is a novel regulator of cellular senescence and inflammaging.
复制标题
DOI：
10.1096/fj.201800965r
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Barnes PJ
中科院分区：
文献类型：
--
作者：
Baker JR;Vuppusetty C;Colley T;Hassibi S;Fenwick PS;Donnelly LE;Ito K;Barnes PJ
加速衰老的疾病经常同时发生（多重发病），并且其患病率不断增加，社会和医疗保健成本高昂。慢性阻塞性肺病 (COPD) 就是其中一种疾病，其中一半的患者患有 ≥ 4 种与年龄相关的疾病。加速衰老疾病具有共同的分子途径，导致衰老细胞的有害积累。这些衰老细胞不再分裂，而是释放多种炎症蛋白，被称为衰老相关的分泌表型，可能使疾病永久存在并加速。在这里，我们发现抑制在 COPD 细胞中增加的 miR-570-3p，可以通过恢复抗衰老分子 Sirtuin-1 来逆转细胞衰老。 MiR-570-3p 通过 p38 MAP 激酶-c-Jun 信号传导由气道上皮细胞中的氧化应激诱导，并通过抑制 Sirtuin-1 来驱动衰老。使用antagomir抑制COPD小气道上皮细胞中升高的miR-570-3p，恢复sirtuin-1并抑制细胞衰老标志物（p16INK4a、p21Waf1和p27Kip1），从而通过细胞周期的进展来恢复细胞生长。 MiR-570-3p 抑制还会抑制衰老相关的分泌表型（基质金属蛋白酶-2/9、C-X-C 基序趋化因子配体 8、IL-1β 和 IL-6）。总的来说，这些数据表明，抑制 miR-570-3p 通过恢复 Sirtuin-1 使细胞恢复活力，减少许多与细胞衰老相关的异常。—Baker, J. R.、Vuppusetty, C.、Colley, T.、Hassibi, S.、Fenwick, P. S.、Donnelly, L. E.、Ito, K.、Barnes, P. J. MicroRNA-570 是一种 细胞衰老和炎症的新型调节剂。
Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs. Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases. Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells. These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease. Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1. MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1. Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle. MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6). Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.—Baker, J. R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P. S., Donnelly, L. E., Ito, K., Barnes, P. J. MicroRNA-570 is a novel regulator of cellular senescence and inflammaging.