聚轮状分子表面的分子运动减轻了间充质干细胞中的氧化应激诱导的衰老。
Molecular Mobility of Polyrotaxane Surfaces Alleviates Oxidative Stress-Induced Senescence in Mesenchymal Stem Cells.
发表日期:2023 Mar 21
作者:
Hiroki Masuda, Yoshinori Arisaka, Masahiro Hakariya, Takanori Iwata, Tetsuya Yoda, Nobuhiko Yui
来源:
MACROMOLECULAR BIOSCIENCE
摘要:
Polyrotaxane是一种超分子组装物,由线型聚合物穿过多个环形分子组成。 Polyrotaxane的一项独特特性是分子可动性,环形分子沿线型聚合物移动。 Polyrotaxane表面分子的分子可动性通过改变是相关蛋白质(YAPs)的亚细胞定位而影响细胞扩展,分化和其他与细胞有关的方面。亚细胞YAP定位与来源于氧化应激的细胞衰老有关,这已知会引起癌症,糖尿病和心脏病。在不同分子运动性的Polyrotaxane表面上培养的人类间充质干细胞(HMSCs)的亚细胞YAP定位和H2O2诱导氧化应激后的细胞衰老的影响进行了评估。氧化应激促进了高运动性Polyrotaxane表面HMSCs的细胞质YAP定位;然而,低运动性Polyrotaxane表面更有效地保持了核YAP定位,表现出低的细胞衰老相关β-半乳糖苷酶活性和衰老相关基因表达和DNA损伤,而高运动性表面则表现出更高的值。这些结果表明,Polyrotaxane表面的分子可动性调节亚细胞YAP定位,从而保护HMSCs免受氧化应激引起的细胞衰老。将Polyrotaxane表面的分子可动性应用于植入支架,可以为预防和治疗由氧化应激引起的疾病提供见解。本文受版权保护。版权所有。
Polyrotaxane is a supramolecular assembly consisting of multiple cyclic molecules threaded by a linear polymer. One of the unique properties of polyrotaxane is the molecular mobility, cyclic molecules moving along the linear polymer. Molecular mobility of polyrotaxane surfaces affect cell spreading, differentiation, and other cell-related aspects through changing subcellular localization of yes-associated proteins (YAPs). Subcellular YAP localization is also related to cell senescence derived from oxidative stress, which is known to cause cancer, diabetes, and heart disease. Here, the effects of polyrotaxane surface molecular mobility on subcellular YAP localization and cell senescence following H2 O2 -induced oxidative stress have been evaluated in human mesenchymal stem cells (HMSCs) cultured on polyrotaxane surfaces with different molecular mobilities. Oxidative stress promotes cytoplasmic YAP localization in HMSCs on high-mobility polyrotaxane surfaces; however, low-mobility polyrotaxane surfaces more effectively maintain nuclear YAP localization, exhibiting lower senescence-associated β-galactosidase activity and senescence-related gene expression and DNA damage than that seen with the high-mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces regulates subcellular YAP localization, thereby protecting HMSCs from oxidative stress-induced cell senescence. Applying the molecular mobility of polyrotaxane surfaces to implantable scaffolds can provide insights into the prevention and treatment of diseases caused by oxidative stress. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.