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阿托伐他汀对骨髓间充质干细胞中血管生成相关基因VEGF-A、HGF和IGF-1的影响以及对PI3K/AKT/mTOR转录本的调节

Effect of Atorvastatin on Angiogenesis-Related Genes VEGF-A, HGF and IGF-1 and the Modulation of PI3K/AKT/mTOR Transcripts in Bone-Marrow-Derived Mesenchymal Stem Cells.

作者信息

Adamičková Adriana, Chomaničová Nikola, Gažová Andrea, Maďarič Juraj, Červenák Zdenko, Valášková Simona, Adamička Matúš, Kyselovic Jan

机构信息

5th Department of Internal Medicine, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.

Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.

出版信息

Curr Issues Mol Biol. 2023 Mar 10;45(3):2326-2337. doi: 10.3390/cimb45030150.

Abstract

Stem cell transplantation represents a unique therapeutic tool in tissue engineering and regenerative medicine. However, it was shown that the post-injection survival of stem cells is poor, warranting a more comprehensive understanding of activated regenerative pathways. Numerous studies indicate that statins improve the therapeutic efficacy of stem cells in regenerative medicine. In the present study, we investigated the effect of the most widely prescribed statin, atorvastatin, on the characteristics and properties of bone-marrow-derived mesenchymal stem cells (BM-MSCs) cultured in vitro. We found that atorvastatin did not decrease the viability of BM-MSCs, nor did it change the expression of MSC cell surface markers. Atorvastatin upregulated the mRNA expression levels of and , whereas the mRNA expression level of was decreased. In addition, the PI3K/AKT signaling pathway was modulated by atorvastatin as indicated by the high mRNA expression levels of and . Moreover, our data revealed the upregulation of mRNA levels; however, no change was observed in the BAX and BCL-2 transcripts. We propose that atorvastatin benefits BM-MSC treatment due to its ability to upregulate angiogenesis-related genes expression and transcripts of the PI3K/AKT/mTOR pathway.

摘要

干细胞移植是组织工程和再生医学中一种独特的治疗手段。然而,研究表明干细胞注射后的存活率较低,这就需要更全面地了解激活的再生途径。大量研究表明,他汀类药物可提高干细胞在再生医学中的治疗效果。在本研究中,我们调查了处方最广泛的他汀类药物阿托伐他汀对体外培养的骨髓间充质干细胞(BM-MSCs)特性的影响。我们发现,阿托伐他汀不会降低BM-MSCs的活力,也不会改变MSC细胞表面标志物的表达。阿托伐他汀上调了 和 的mRNA表达水平,而 的mRNA表达水平则下降。此外,阿托伐他汀调节了PI3K/AKT信号通路, 和 的高mRNA表达水平表明了这一点。此外,我们的数据显示 mRNA水平上调;然而,BAX和BCL-2转录本未观察到变化。我们认为,阿托伐他汀有利于BM-MSC治疗,因为它能够上调血管生成相关基因的表达以及PI3K/AKT/mTOR途径的转录本。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2fe/10046955/0acca41406ee/cimb-45-00150-g001.jpg

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