miR-10a restores human mesenchymal stem cell differentiation by repressing KLF4.
miR-10a restores human mesenchymal stem cell differentiation by repressing KLF4.
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DOI：
10.1002/jcp.24402
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发表时间：
2013-12
影响因子：
5.6
通讯作者：
Liu, Shi-Ming
中科院分区：
文献类型：
--
作者：
Li, Jiao;Dong, Jun;Zhang, Zhen-Hui;Zhang, Dong-Cheng;You, Xiang-Yu;Zhong, Yun;Chen, Min-Sheng;Liu, Shi-Ming
miRNAs最近被证明在人类衰老中发挥重要作用。然而，证明衰老相关的miRNA在人类间充质干细胞（hMSC）中的作用的数据是有限的。我们观察到hMSC分化随着年龄的增长而下降。我们还通过比较来自年轻和老年个体的hMSCs的miRNA表达，发现miR-10a的表达随着年龄的增长而显著降低。因此，我们推测miR-10a的下调可能与来自老年个体的hMSCs的分化能力降低有关。慢病毒构建体用于上调或下调年轻和老年hMSC中的miR-10a。miR-10a的上调导致向成脂、成骨和成软骨谱系的分化增加以及细胞衰老减少。相反，下调miR-10a导致细胞分化减少和细胞衰老增加。产生嵌合荧光素酶报告系统，其用KLF 4的全长3′-UTR区域标记，所述KLF 4的全长3′-UTR区域含有具有或不具有四个核苷酸突变的种子匹配序列。将这些构建体与miR-10a模拟物共转染到细胞中。荧光素酶活性被miR-10a模拟物显著抑制，证明miR-10a与KLF 4的3′-UTR直接结合。直接抑制衰老hMSC中的KLF 4可增加细胞分化并减少细胞衰老。总之，miR-10a通过抑制KLF 4恢复老化hMSCs的分化能力。衰老相关的miRNAs可能在修复衰老引起的细胞功能障碍方面具有广泛的应用。J.细胞。228：2324-2336，2013。©作者。出版社：Wiley Periodicals，Inc.
miRNAs have recently been shown to play a significant role in human aging. However, data demonstrating the effects of aging-related miRNAs in human mesenchymal stem cells (hMSCs) are limited. We observed that hMSC differentiation decreased with aging. We also identified that miR-10a expression was significantly decreased with age by comparing the miRNA expression of hMSCs derived from young and aged individuals. Therefore, we hypothesized that the downregulation of miR-10a may be associated with the decreased differentiation capability of hMSCs from aged individuals. Lentiviral constructs were used to up- or downregulate miR-10a in young and old hMSCs. Upregulation of miR-10a resulted in increased differentiation to adipogenic, osteogenic, and chondrogenic lineages and in reduced cell senescence. Conversely, downregulation of miR-10a resulted in decreased cell differentiation and increased cell senescence. A chimeric luciferase reporter system was generated, tagged with the full-length 3′-UTR region of KLF4 harboring the seed-matched sequence with or without four nucleotide mutations. These constructs were cotransfected with the miR-10a mimic into cells. The luciferase activity was significantly repressed by the miR-10a mimic, proving the direct binding of miR-10a to the 3′-UTR of KLF4. Direct suppression of KLF4 in aged hMSCs increased cell differentiation and decreased cell senescence. In conclusion, miR-10a restores the differentiation capability of aged hMSCs through repression of KLF4. Aging-related miRNAs may have broad applications in the restoration of cell dysfunction caused by aging. J. Cell. Physiol. 228: 2324–2336, 2013. © The Authors. Published by Wiley Periodicals, Inc.
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艾姆斯侏儒小鼠肝脏中的 MicroRNA 调节可能有助于延缓衰老。
影响因子：
7.8
作者：
Bates DJ;Li N;Liang R;Sarojini H;An J;Masternak MM;Bartke A;Wang E
通讯作者：
Wang E
影响因子：
--
作者：
Kretlow JD;Jin YQ;Liu W;Zhang WJ;Hong TH;Zhou G;Baggett LS;Mikos AG;Cao Y
通讯作者：
Cao Y
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
--
作者：
Mendes, SC;Tibbe, JM;Van Blitterswijk, CA
通讯作者：
Van Blitterswijk, CA
影响因子：
5.2
作者：
Baxter, MA;Wynn, RF;Bellantuono, I
通讯作者：
Bellantuono, I