牙髓干细胞来源的外泌体通过调节Nrf2-keap1/GPX4信号通路抑制铁凋亡,改善慢性肾脏疾病损伤。

IF 2.7 4区 生物学 Q1 ANATOMY & MORPHOLOGY Tissue & cell Pub Date : 2024-12-06 DOI:10.1016/j.tice.2024.102670
Lin Luo, Jing Wang, Jie Zhao, Bin Yang, Wenzhe Ma, Jiaru Lin
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引用次数: 0

摘要

长期以来,慢性肾脏疾病(CKD)一直是一个重大的全球健康挑战。遗憾的是,目前的治疗干预措施在阻止CKD进展方面表现出有限的功效。大量证据表明,铁下垂可能在CKD中起关键作用。牙髓干细胞源性外泌体(DPSC-Exos)具有来源丰富、免疫原性低等优点,在慢性肾病治疗中具有广阔的应用前景。方法:建立小鼠CKD模型,观察DPSC-Exos对CKD的治疗作用。首先,我们成功地提取并鉴定了DPSC-Exos。然后将小鼠随机分为sham组、PBS组、CKD组和CKD+Exos组。我们的研究检测了各组中凋亡相关途径分子Nrf2、GPX4、Keap1和HO-1的表达。最后,我们检测了炎症因子TNF-α、IL-1β和IL-6在损伤部位的表达水平。结果:小鼠经DPSC-Exos处理后,铁下沉抑制因子Nrf2及其下游调控因子GPX4、HO-1的表达增加,而Keap1的表达降低。TNF-α、IL-1β、IL-6的表达也降低。结论:DPSC-Exos可能通过Keap1-Nrf2/GPX4通路抑制铁上沉,降低损伤部位的炎症反应,揭示其对CKD的潜在治疗作用。
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Dental pulp stem cells derived exosomes inhibit ferroptosis via regulating the Nrf2-keap1/GPX4 signaling pathway to ameliorate chronic kidney disease injury.

Introduction: Chronic kidney disease (CKD) has long represented a substantial global health challenge. Regrettably, current therapeutic interventions exhibit limited efficacy in halting the progression of CKD. Ferroptosis may play a crucial role in CKD, as indicated by substantial evidence. Dental pulp stem cell-derived exosomes (DPSC-Exos) possess advantages such as abundant sources and low immunogenicity, holding promising prospects in CKD treatment.

Methods: This study constructed a mouse CKD model to investigate the therapeutic effects of DPSC-Exos. First, we successfully extracted and identified DPSC-Exos. Then, mice were randomly divided into sham, PBS, CKD, and CKD+Exos groups. Our study determined the expression of ferroptosis-related pathway molecules Nrf2, GPX4, Keap1, and HO-1 in each group. Finally, we detected the expression levels of inflammatory factors, TNF-α, IL-1β, and IL-6, at the injury site.

Results: Mice treated with DPSC-Exos showed increased expression of the ferroptosis inhibitory factor Nrf2 and its downstream regulatory factors GPX4 and HO-1, while the expression of Keap1 decreased. The expression of TNF-α, IL-1β, and IL-6 also decreased.

Conclusion: DPSC-Exos may help inhibit ferroptosis through the Keap1-Nrf2/GPX4 pathway and reduce the inflammatory response at the injury site, revealing their potential therapeutic effects on CKD.

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来源期刊
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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