砷与代谢性疾病：来自间充质干细胞的新见解。

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-03-11 DOI:10.1016/j.taap.2025.117299

Yuxin Hu , Jialin He , Yue Ma , Lili Ge , Bin Lou , Xin Fang , Huihui Wang , Yuanyuan Xu

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引用次数: 0

摘要

砷是环境中常见的有毒金属污染物。人类通过饮用水、空气、食物和医疗接触到砷。长期接触砷是2型糖尿病的危险因素，也是骨质疏松和肥胖的潜在危险因素。间充质干细胞（Mesenchymal stem cells, MSCs）是具有多向分化潜能和免疫调节能力的成体干细胞。这些细胞通过分化为受损组织的实质细胞（如胰岛样细胞和成骨细胞）和抵抗慢性炎症，在代谢性疾病的实验研究中显示出治疗潜力。同时，当MSCs中的关键功能基因被抑制时，实验动物表现出与代谢疾病相关的变化，如胰岛素抵抗和肥胖。砷暴露抑制间充质干细胞的分化能力，导致免疫调节因子的合成和分泌改变，诱导细胞衰老和凋亡。因此，MSCs的功能障碍和死亡可能是砷相关代谢疾病的重要发病机制。MSCs在砷相关代谢疾病中的功能变化以及MSCs在砷发病机制中的作用值得进一步研究。此外，砷诱导间充质干细胞功能障碍的机制有待深入探讨。

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Arsenic and metabolic diseases: New insights from mesenchymal stem cells

Arsenic is a common toxic metal contaminant in the environment. Humans are exposed to arsenic through drinking water, air, food, and medical treatment. Chronic exposure to arsenic is a well-documented risk factor of type 2 diabetes and a potential risk factor of osteoporosis and obesity. Mesenchymal stem cells (MSCs) are adult stem cells with multiple differentiation potential and immunomodulatory capacity. These cells have shown therapeutic potential in experimental studies of metabolic diseases by differentiating into parenchymal cells of damaged tissues, such as islet-like cells and osteoblasts, and resisting chronic inflammation. Meanwhile, when key functional genes were suppressed in MSCs, experimental animals showed metabolic disease-related changes, such as insulin resistance and obesity. Arsenic exposure inhibits the differentiation capacity of MSCs, leads to changes in the synthesis and secretion of immunomodulatory factors, and induces cellular senescence and apoptosis. Therefore, dysfunction and death of MSCs may be important pathogenesis of arsenic-related metabolic diseases. Future studies on the functional changes of MSCs in arsenic-related metabolic diseases and the role of MSCs in arsenic pathogenesis are worthwhile. In addition, the mechanism of arsenic-induced dysfunction in MSCs needs to be explored in depth.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.