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miR-10a 通过 KLF4 使衰老的人类间充质干细胞年轻化并改善心肌梗死后的心脏功能。

miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4.

机构信息

Guangzhou Institute of Cardiovascular Disease, Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

Department of Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

出版信息

Stem Cell Res Ther. 2018 May 30;9(1):151. doi: 10.1186/s13287-018-0895-0.

DOI:10.1186/s13287-018-0895-0
PMID:29848383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5977543/
Abstract

BACKGROUND

Aging is one of the key factors that regulate the function of human bone marrow mesenchymal stem cells (hBM-MSCs) and related changes in microRNA (miRNA) expression. However, data reported on aging-related miRNA changes in hBM-MSCs are limited.

METHODS

We demonstrated previously that miR-10a is significantly decreased in aged hBM-MSCs and restoration of the miR-10a level attenuated cell senescence and increased the differentiation capacity of aged hBM-MSCs by repressing Krüpple-like factor 4 (KLF4). In the present study, miR-10a was overexpressed or KLF4 was downregulated in old hBM-MSCs by lentiviral transduction. The hypoxia-induced apoptosis, cell survival, and cell paracrine function of aged hBM-MSCs were investigated in vitro. In vivo, miR-10a-overexpressed or KLF4-downregulated old hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI). The mouse cardiac function of cardiac angiogenesis was measured and cell survival of aged hBM-MSCs was investigated.

RESULTS

Through lentivirus-mediated upregulation of miR-10a and downregulation of KLF4 in aged hBM-MSCs in vitro, we revealed that miR-10a decreased hypoxia-induced cell apoptosis and increased cell survival of aged hBM-MSCs by repressing the KLF4-BAX/BCL2 pathway. In vivo, transplantation of miR-10a-overexpressed aged hBM-MSCs promoted implanted stem cell survival and improved cardiac function after MI. Mechanistic studies revealed that overexpression of miR-10a in aged hBM-MSCs activated Akt and stimulated the expression of angiogenic factors, thus increasing angiogenesis in ischemic mouse hearts.

CONCLUSIONS

miR-10a rejuvenated aged hBM-MSCs which improved angiogenesis and cardiac function in injured mouse hearts.

摘要

背景

衰老是调节人类骨髓间充质干细胞（hBM-MSCs）功能的关键因素之一，相关的 microRNA（miRNA）表达变化也随之发生。然而，关于 hBM-MSCs 衰老相关 miRNA 变化的数据有限。

方法

我们之前已经证明，miR-10a 在衰老的 hBM-MSCs 中显著降低，并且恢复 miR-10a 水平通过抑制 Krüpple 样因子 4（KLF4）来减弱细胞衰老并增加衰老的 hBM-MSCs 的分化能力。在本研究中，通过慢病毒转导在老年 hBM-MSCs 中过表达 miR-10a 或下调 KLF4。在体外研究了衰老的 hBM-MSCs 的缺氧诱导凋亡、细胞存活和细胞旁分泌功能。在体内，将过表达 miR-10a 或下调 KLF4 的老年 hBM-MSCs 植入心肌梗死（MI）后的梗死小鼠心脏。测量了小鼠心脏的血管生成功能和衰老的 hBM-MSCs 的细胞存活情况。

结果

通过慢病毒介导的 miR-10a 在体外上调和 KLF4 在衰老的 hBM-MSCs 中的下调，我们揭示了 miR-10a 通过抑制 KLF4-BAX/BCL2 途径减少缺氧诱导的细胞凋亡并增加衰老的 hBM-MSCs 的细胞存活。在体内，过表达 miR-10a 的老年 hBM-MSCs 的移植促进了植入干细胞的存活，并改善了 MI 后的心脏功能。机制研究表明，在衰老的 hBM-MSCs 中过表达 miR-10a 激活了 Akt 并刺激了血管生成因子的表达，从而增加了缺血小鼠心脏的血管生成。

结论

miR-10a 使衰老的 hBM-MSCs 恢复活力，改善了受伤小鼠心脏的血管生成和心脏功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/5af8ca547d98/13287_2018_895_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/cc090e115a81/13287_2018_895_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/73d28cb17c56/13287_2018_895_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/fca1f7b2e5d8/13287_2018_895_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/a0d6d30d4e85/13287_2018_895_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/2a60b5c11ed8/13287_2018_895_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/6f7b9f09168b/13287_2018_895_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/29d02a3b6a4f/13287_2018_895_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/5af8ca547d98/13287_2018_895_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/cc090e115a81/13287_2018_895_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/73d28cb17c56/13287_2018_895_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/fca1f7b2e5d8/13287_2018_895_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/a0d6d30d4e85/13287_2018_895_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/2a60b5c11ed8/13287_2018_895_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/6f7b9f09168b/13287_2018_895_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/29d02a3b6a4f/13287_2018_895_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e2/5977543/5af8ca547d98/13287_2018_895_Fig8_HTML.jpg

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本文引用的文献

1
Krüppel-like factor 4 (KLF4): What we currently know.Krüppel样因子4（KLF4）：我们目前所了解的情况。
Gene. 2017 May 5;611:27-37. doi: 10.1016/j.gene.2017.02.025. Epub 2017 Feb 22.
2
Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination.增殖、存活与代谢：PI3K/AKT/mTOR信号通路在多能性及细胞命运决定中的作用
Development. 2016 Sep 1;143(17):3050-60. doi: 10.1242/dev.137075.
3
Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy.
基因修饰间充质基质细胞：一种细胞疗法，能在心肌梗死后提供更有效的修复。
Stem Cell Res Ther. 2024 Sep 27;15(1):323. doi: 10.1186/s13287-024-03942-7.
4
Genetic variants and mRNA expression levels of and with hypertension: A combination of case-control study and cohort study.与高血压相关的基因变异及mRNA表达水平：病例对照研究与队列研究相结合
J Biomed Res. 2024 Aug 27;39(1):103-113. doi: 10.7555/JBR.38.20240208.
5
MSC-Based Cell Therapy in Neurological Diseases: A Concise Review of the Literature in Pre-Clinical and Clinical Research.基于间充质干细胞的神经疾病细胞治疗：临床前和临床研究文献的简明综述。
Biomolecules. 2024 Apr 30;14(5):538. doi: 10.3390/biom14050538.
6
Unlocking the dark matter: noncoding RNAs and RNA modifications in cardiac aging.揭示暗物质：心脏衰老中的非编码 RNA 和 RNA 修饰。
Am J Physiol Heart Circ Physiol. 2024 Mar 1;326(3):H832-H844. doi: 10.1152/ajpheart.00532.2023. Epub 2024 Feb 2.
7
TRAF3IP2 drives mesenchymal stem cell senescence via regulation of NAMPT-mediated NAD biosynthesis.TRAF3IP2通过调节NAMPT介导的NAD生物合成来驱动间充质干细胞衰老。
Heliyon. 2023 Aug 29;9(9):e19505. doi: 10.1016/j.heliyon.2023.e19505. eCollection 2023 Sep.
8
Knockdown of long noncoding RNA SAN rejuvenates aged adipose-derived stem cells via miR-143-3p/ADD3 axis.长链非编码 RNA SAN 的敲低通过 miR-143-3p/ADD3 轴使衰老的脂肪来源干细胞恢复活力。
Stem Cell Res Ther. 2023 Aug 21;14(1):213. doi: 10.1186/s13287-023-03441-1.
9
Effects of microenvironment and biological behavior on the paracrine function of stem cells.微环境和生物学行为对干细胞旁分泌功能的影响。
Genes Dis. 2023 Apr 11;11(1):135-147. doi: 10.1016/j.gendis.2023.03.013. eCollection 2024 Jan.
10
miR-10a-3p modulates adiposity and suppresses adipose inflammation through TGF-β1/Smad3 signaling pathway.miR-10a-3p 通过 TGF-β1/Smad3 信号通路调节体脂和抑制脂肪组织炎症。
Front Immunol. 2023 Jun 2;14:1213415. doi: 10.3389/fimmu.2023.1213415. eCollection 2023.
源自羊水干细胞的外泌体miR-10a在化疗后可保护卵巢卵泡。
Sci Rep. 2016 Mar 16;6:23120. doi: 10.1038/srep23120.
4
Krüppel-like factor 4 induces apoptosis and inhibits tumorigenic progression in SK-BR-3 breast cancer cells.Krüppel 样因子 4 诱导 SK-BR-3 乳腺癌细胞凋亡并抑制肿瘤发生进展。
FEBS Open Bio. 2015 Mar 2;5:147-54. doi: 10.1016/j.fob.2015.02.003. eCollection 2015.
5
microRNA-378 promotes mesenchymal stem cell survival and vascularization under hypoxic-ischemic conditions in vitro.微小RNA-378在体外缺氧缺血条件下促进间充质干细胞存活和血管生成。
Stem Cell Res Ther. 2014 Nov 23;5(6):130. doi: 10.1186/scrt520.
6
Stromal derived factor 1α: a chemokine that delivers a two-pronged defence of the myocardium.基质衍生因子1α：一种为心肌提供双管防御的趋化因子。
Pharmacol Ther. 2014 Sep;143(3):305-15. doi: 10.1016/j.pharmthera.2014.03.009. Epub 2014 Apr 1.
7
C1q tumor necrosis factor-related protein-3 protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis through the phosphoinositide 3-kinase/Akt pathway.C1q 肿瘤坏死因子相关蛋白-3 通过磷酸肌醇 3-激酶/蛋白激酶 B 通路保护间充质干细胞免受低氧和血清剥夺诱导的细胞凋亡。
Int J Mol Med. 2014 Jan;33(1):97-104. doi: 10.3892/ijmm.2013.1550. Epub 2013 Nov 7.
8
Contrasting effects of Krüppel-like factor 4 on X-ray-induced double-strand and single-strand DNA breaks in mouse astrocytes.Krüppel 样因子 4 对 X 射线诱导的小鼠星形胶质细胞双链和单链 DNA 断裂的对比影响。
Cell Biochem Funct. 2014 Apr;32(3):241-8. doi: 10.1002/cbf.3007. Epub 2013 Sep 20.
9
Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression.慢病毒载体介导的热休克蛋白 27 表达增强了梗死心脏中的间充质干细胞存活。
Hum Gene Ther. 2013 Oct;24(10):840-51. doi: 10.1089/hum.2011.009.
10
MicroRNAs: new candidates for the regulation of the human cumulus-oocyte complex.微小 RNA：人卵丘-卵母细胞复合物调控的新候选分子。
Hum Reprod. 2013 Nov;28(11):3038-49. doi: 10.1093/humrep/det321. Epub 2013 Jul 30.