CXCL2 Impairs Functions of Bone Marrow Mesenchymal Stem Cells and Can Serve as a Serum Marker in High-Fat Diet-Fed Rats.
CXCL2 Impairs Functions of Bone Marrow Mesenchymal Stem Cells and Can Serve as a Serum Marker in High-Fat Diet-Fed Rats.
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CXCL2 损害骨髓间充质干细胞的功能并可作为高脂肪饮食喂养大鼠的血清标记物
DOI：
10.3389/fcell.2021.687942
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发表时间：
2021
影响因子：
5.5
通讯作者：
Xiao R
中科院分区：
文献类型：
--
作者：
Bi J;Li Q;Yang Z;Cai L;Lv T;Yang X;Yan L;Liu X;Wang Q;Fu X;Xiao R
在现代社会中，过度食用高脂肪饮食（HFD）是许多疾病（如糖尿病、骨关节炎和某些癌症）的重要危险因素。解决手足口病相关疾病的细胞和分子机制对人类健康具有重要意义。间充质干细胞（MSCs）在组织稳态中起着关键作用，并受到长时间高脂肪喂养的不利影响。HFD诱导的低度全身性炎症的特征是促炎细胞因子水平升高，并改变许多器官的内稳态。然而，HFD相关的炎症细胞因子是否、哪些以及如何损害MSCs仍不清楚。在这里，我们证明了HFD诱导血清细胞因子紊乱，特别是大鼠血清CXCL2水平的持续升高。与之相对应的是，HFD大鼠功能受损的骨髓间充质干细胞（BMSCs）的差异表达基因（DEGs）富集于细胞因子信号。进一步的机制分析表明，体外CXCL2处理通过激活Rac1抑制骨髓间充质干细胞的成脂潜能，并分别通过诱导ELMO1和活性氧（ROS）的过量产生促进骨髓间充质干细胞的迁移和衰老。此外，我们发现虽然糖脂代谢指标可以得到纠正，但饮食矫正和抗炎阿司匹林治疗并不能完全挽救CXCL2升高和BMSC功能障碍，这表明HFD对血清CXCL2水平和BMSC功能的有害影响是持久的。总之，我们的研究结果确定了CXCL2在骨髓间充质干细胞功能中是一个重要的调节因子，并且可能作为一种血清标记物来指示HFD诱导的骨髓间充质干细胞功能障碍。此外，我们的研究结果强调了高脂肪摄入、慢性炎症和BMSC功能障碍之间的复杂联系，这可能促进HFD相关疾病保护策略的发展。
In modern society excessive consumption of a high-fat diet (HFD) is a significant risk factor for many diseases such as diabetes, osteoarthritis and certain cancers. Resolving cellular and molecular mechanisms underlying HFD-associated disorders is of great importance to human health. Mesenchymal stem cells (MSCs) are key players in tissue homeostasis and adversely affected by prolonged HFD feeding. Low-grade systemic inflammation induced by HFD is characterized by increased levels of pro-inflammatory cytokines and alters homeostasis in many organs. However, whether, which and how HFD associated inflammatory cytokines impair MSCs remain unclear. Here we demonstrated that HFD induced serum cytokines disturbances, especially a continuous elevation of serum CXCL2 level in rats. Coincidentally, the differentially expressed genes (DEGs) of bone marrow MSCs (BMSCs) which functions were impaired in HFD rats were enriched in cytokine signaling. Further mechanism analysis revealed that CXCL2 treatment in vitro suppresses the adipogenic potential of BMSCs via Rac1 activation, and promoted BMSC migration and senescence by inducing over-production of ELMO1 and reactive oxygen species (ROS) respectively. Moreover, we found that although glycolipid metabolism indicators can be corrected, the CXCL2 elevation and BMSC dysfunctions cannot be fully rescued by diet correction and anti-inflammatory aspirin treatment, indicating the long-lasting deleterious effects of HFD on serum CXCL2 levels and BMSC functions. Altogether, our findings identify CXCL2 as an important regulator in BMSCs functions and may serve as a serum marker to indicate the BMSC dysfunctions induced by HFD. In addition, our findings underscore the intricate link among high-fat intake, chronic inflammation and BMSC dysfunction which may facilitate development of protective strategies for HFD associated diseases.
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影响因子：
3.3
作者：
Gao, Xiu-ren;Adhikari, Chandar M.;Zuo, Zhi-yi
通讯作者：
Zuo, Zhi-yi
影响因子：
4
作者：
Kimbrel, Erin A.;Kouris, Nicholas A.;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
4.3
作者：
Klimczak A;Kozlowska U
通讯作者：
Kozlowska U
DOI：
10.1179/096805102125000092
发表时间：
2002-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Calkins, CM;Bensard, DD;McIntyre, RC
通讯作者：
McIntyre, RC
DOI：
10.1159/000358901
发表时间：
2014-01-01
期刊：
AGING: FACTS AND THEORIES
影响因子：
--
作者：
Kong, Yahui;Trabucco, Sally E.;Zhang, Hong
通讯作者：
Zhang, Hong