Elastin-derived peptides (EDPs) affect gene and protein expression in human mesenchymal stem cells (hMSCs) – preliminary study

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-08-05 DOI:10.1016/j.cyto.2024.156725
Konrad A. Szychowski, Bartosz Skóra
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Abstract

During the aging process, elastin is degraded and the level of elastin-derived peptides (EDPs) successively increases. The main peptide released from elastin during its degradation is a peptide with the VGVAPG sequence. To date, several papers have described that EDPs or elastin-like peptides (ELPs) affect human mesenchymal stem cells (hMSCs) derived from different tissues. Unfortunately, despite the described effect of EDPs or ELPs on the hMSC differentiation process, the mechanism of action of these peptides has not been elucidated. Therefore, the aim of the present study was to evaluate the impact of the VGVAPG and VVGPGA peptides on the hMSC stemness marker and elucidation of the mechanism of action of these peptides. Our data show that both studied peptides (VGVAPG and VVGPGA) act with the involvement of ERK1/2 and c-SRC kinases. However, their mechanism of activation is probably different in hMSCs derived from adipose tissue. Both studied peptides increase the KI67 protein level in hMSCs, but this is not accompanied with cell proliferation. Moreover, the changes in the NANOG and c-MYC protein expression and in the SOX2 and POU5F1 mRNA expression suggest that EDPs reduced the hMSC stemness properties and could initiate cell differentiation. The initiation of differentiation was evidenced by changes in the expression of AhR and PPARγ protein as well as specific genes (ACTB, TUBB3) and proteins (β-actin, RhoA) involved in cytoskeleton remodeling. Our data suggest that the presence of EDPs in tissue can initiate hMSC differentiation into more tissue-specific cells.

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弹性蛋白衍生肽(EDPs)影响人类间充质干细胞(hMSCs)的基因和蛋白质表达--初步研究。
在衰老过程中,弹性蛋白会发生降解,弹性蛋白衍生肽(EDPs)的含量也会随之增加。弹性蛋白降解过程中释放的主要肽是一种具有 VGVAPG 序列的肽。迄今为止,已有多篇论文描述了EDPs或弹性蛋白样肽(ELPs)对来自不同组织的人类间充质干细胞(hMSCs)的影响。遗憾的是,尽管EDPs或ELPs对hMSC分化过程有影响,但这些肽的作用机制尚未阐明。因此,本研究旨在评估VGVAPG和VVGPGA肽对hMSC干性标志物的影响,并阐明这些肽的作用机制。我们的数据显示,所研究的两种肽(VGVAPG 和 VVGPGA)都在 ERK1/2 和 c-SRC 激酶的参与下发挥作用。不过,它们在源自脂肪组织的 hMSCs 中的激活机制可能有所不同。所研究的两种肽都能增加 hMSCs 中的 KI67 蛋白水平,但这并不伴随细胞增殖。此外,NANOG和c-MYC蛋白表达以及SOX2和POU5F1 mRNA表达的变化表明,EDPs降低了hMSC干性特性,并能启动细胞分化。AhR和PPARγ蛋白以及参与细胞骨架重塑的特定基因(ACTB、TUBB3)和蛋白(β-肌动蛋白、RhoA)的表达变化证明了分化的启动。我们的数据表明,组织中存在的 EDPs 能促使 hMSC 分化为更具组织特异性的细胞。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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