Aspirin attenuates the detrimental effects of TNF-α on BMMSC stemness by modulating the YAP-SMAD7 axis.

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2024-08-16 DOI:10.1186/s10020-024-00890-z

Xudong Wang, Yong Liu, Shiyong Zhang, Linli Zheng, Yunze Kang, Puyi Sheng, Ziji Zhang

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引用次数: 0

Abstract

Background: Bone marrow mesenchymal stem cells (BMMSCs) are commonly used for cell transplantation to treat refractory diseases. However, the presence of inflammatory factors, such as tumour necrosis factor-alpha (TNF-α), at the transplantation site severely compromises the stemness of BMMSCs, thereby reducing the therapeutic effect of cell transplantation. Aspirin (AS) is a drug that has been in use for over a century and has a wide range of effects, including the regulation of cell proliferation, multidirectional differentiation, and immunomodulatory properties of stem cells. However, it is still unclear whether AS can delay the damaging effects of TNF-α on BMMSC stemness.

Methods: This study investigated the effects of AS and TNF-α on BMMSC stemness and the molecular mechanisms using colony formation assay, western blot, qRT-PCR, and overexpression or knockdown of YAP and SMAD7.

Results: The results demonstrated that TNF-α inhibited cell proliferation, the expression of stemness, osteogenic and chondrogenic differentiation markers of BMMSCs. Treatment with AS was shown to mitigate the TNF-α-induced damage to BMMSC stemness. Mechanistic studies revealed that AS may reverse the damage caused by TNF-α on BMMSC stemness by upregulating YAP and inhibiting the expression of SMAD7.

Conclusion: AS can attenuate the damaging effects of TNF-α on BMMSC stemness by regulating the YAP-SMAD7 axis. These findings are expected to promote the application of AS to improve the efficacy of stem cell therapy.

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阿司匹林通过调节 YAP-SMAD7 轴减轻 TNF-α 对 BMMSC 干性的有害影响。

背景：骨髓间充质干细胞（BMMSCs）通常用于细胞移植治疗难治性疾病。然而，移植部位存在的肿瘤坏死因子-α（TNF-α）等炎症因子会严重损害骨髓间充质干细胞的干性，从而降低细胞移植的治疗效果。阿司匹林（AS）是一种已使用了一个多世纪的药物，具有广泛的作用，包括调节细胞增殖、多向分化和干细胞的免疫调节特性。然而，AS能否延缓TNF-α对BMMSC干细胞的破坏作用仍不清楚：本研究采用集落形成试验、Western印迹、qRT-PCR、过表达或敲除YAP和SMAD7等方法，研究了AS和TNF-α对BMMSC干性的影响及其分子机制：结果表明：TNF-α抑制了BMMSCs的细胞增殖、干性表达、成骨和软骨分化标志物。AS能减轻TNF-α对BMMSC干性的损伤。机理研究显示，AS可通过上调YAP和抑制SMAD7的表达来逆转TNF-α对BMMSC干性的损伤：AS可通过调节YAP-SMAD7轴，减轻TNF-α对BMMSC干性的损伤作用。这些发现有望促进AS的应用，提高干细胞疗法的疗效。

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

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.