Extracellular vesicles propagate aging in COPD airway epithelial cells by transfer of microRNA-34a
Extracellular vesicles propagate aging in COPD airway epithelial cells by transfer of microRNA-34a
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细胞外囊泡通过 microRNA-34a 的转移促进 COPD 气道上皮细胞的衰老
DOI：
10.1101/2023.12.18.572220
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Devulder J
中科院分区：
文献类型：
--
作者：
Devulder J
慢性阻塞性肺疾病（COPD）与肺老化加速有关，这可以通过肺组织中衰老细胞的积累来证明。MicroRNA (miR)-34a通过抑制关键的抗衰老分子sirtuin-1 （SIRT1）诱导衰老。衰老细胞将衰老扩散到邻近和远处的细胞，这有利于COPD及其合并症的进展。衰老扩散的机制尚不清楚，但可能是通过细胞外囊泡中microrna的转移介导的。目的分析COPD患者细胞外囊泡miRNA含量及其对健康细胞衰老的影响。方法从健康供体或COPD患者气道小上皮细胞（SAEC）中分离sev。用ev培养健康受体SAEC，检测miR-34a以及细胞衰老标志物p21cip1和SIRT1的表达。来自COPD细胞的tsev通过miR-34a的选择性转移诱导健康受体细胞衰老。我们发现，COPD SAEC产生的富含miR-34a的ev数量增加。EVs被健康细胞吸收，导致抗衰老分子sirtuin-1的表达减少，衰老标志物（如p21cip1）的表达增加，衰老相关β-半乳糖苷的阳性染色。结论我们的发现为EVs通过miR-34a而不是通过可溶性介质在人原代细胞中传播细胞衰老的机制提供了证据。富含miR-34a的ev可能会局部传播衰老，导致疾病进展，但也提供了一种远处传播的机制，以解释老年人的合共病和多病。
RationaleChronic obstructive pulmonary disease (COPD) is associated with the acceleration of lung aging, demonstrated by the accumulation of senescent cells in lung tissue. MicroRNA (miR)-34a is induces senescence by suppressing the key anti-aging molecule, sirtuin-1 (SIRT1). Senescent cells spread senescence to neighboring and distant cells, which favors the progression of COPD and its comorbidities. The mechanisms for spreading senescence remain undetermined but may be mediated by the transfer of microRNAs in extracellular vesicles.ObjectivesTo analyze the miRNA content of extracellular vesicles in COPD and explore their effect on cellular senescence of healthy cellsMethodsEVs were isolated from small airway epithelial cells (SAEC) from healthy donors or COPD patients. Recipient healthy SAEC were cultured with EVs and the expression of miR-34a and markers of cellular senescence, p21CIP1and SIRT1, were measured.Main ResultsEVs from COPD cells induce senescence in healthy recipient cells via the selective transfer of miR-34a. We showed that COPD SAEC produce increased numbers of EVs enriched with miR-34a. EVs are taken up by healthy cells, resulting in reduced expression of the anti-aging molecule sirtuin-1 and increased expression of markers of senescence, such as p21CIP1and positive staining for senescence-associated β-galactosidaseConclusionsOur findings provide evidence of the mechanism by which EVs spread cellular senescence in human primary cells via miR-34a, rather than via soluble mediators. EVs enriched with miR-34a may spread senescence locally, accounting for disease progression, but also provide a mechanism for distant spread to account for comorbidities and multimorbidity of the elderly.
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DOI：
10.2147/copd.s99547
发表时间：
2016
影响因子：
2.8
作者：
Lacedonia D;Carpagnano GE;Trotta T;Palladino GP;Panaro MA;Zoppo LD;Foschino Barbaro MP;Porro C
通讯作者：
Porro C
影响因子：
4.6
作者：
Eitan E;Green J;Bodogai M;Mode NA;Bæk R;Jørgensen MM;Freeman DW;Witwer KW;Zonderman AB;Biragyn A;Mattson MP;Noren Hooten N;Evans MK
通讯作者：
Evans MK
影响因子：
8.3
作者：
MacNee, William
通讯作者：
MacNee, William
上皮细胞衰老参与 IPF 发病机制。
DOI：
--
发表时间：
2009
期刊：
影响因子：
--
作者：
Sasaki T;Nakayama K;et al
通讯作者：
et al
影响因子：
29
作者：
Wiley CD;Velarde MC;Lecot P;Liu S;Sarnoski EA;Freund A;Shirakawa K;Lim HW;Davis SS;Ramanathan A;Gerencser AA;Verdin E;Campisi J
通讯作者：
Campisi J