Szychowski Konrad A, Skóra Bartosz
Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, St. Sucharskiego 2, 35-225 Rzeszow, Poland.
Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, St. Sucharskiego 2, 35-225 Rzeszow, Poland.
Cytokine. 2024 Oct;182:156725. doi: 10.1016/j.cyto.2024.156725. Epub 2024 Aug 5.
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.
在衰老过程中，弹性蛋白会降解，弹性蛋白衍生肽（EDPs）的水平会相继升高。弹性蛋白在降解过程中释放的主要肽段是具有VGVAPG序列的肽。迄今为止，已有多篇论文描述了EDPs或类弹性蛋白肽（ELPs）对源自不同组织的人间充质干细胞（hMSCs）的影响。遗憾的是，尽管已描述了EDPs或ELPs对hMSC分化过程的影响，但这些肽的作用机制尚未阐明。因此，本研究的目的是评估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。我们的数据表明，两种研究肽（VGVAPG和VVGPGA）的作用都涉及ERK1/2和c-SRC激酶。然而，它们在源自脂肪组织的hMSCs中的激活机制可能不同。两种研究肽均增加了hMSCs中KI67蛋白的水平，但这并未伴随细胞增殖。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的干性特性，并可能启动细胞分化。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）表达的变化证明了分化的启动。我们的数据表明，组织中EDPs的存在可启动hMSC分化为更多组织特异性细胞。
