Reprogramming of Hypoxia-Induced Metabolic Disorder in Mouse Kidneys by Mesenchymal Stem Cells Through Improving Mitochondrial Dynamics and Function

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-05-13 DOI:10.1002/jbt.70291

Yanjun Wang, Yanling Ding, Tana Wuren, Pengli Luo

{"title":"Reprogramming of Hypoxia-Induced Metabolic Disorder in Mouse Kidneys by Mesenchymal Stem Cells Through Improving Mitochondrial Dynamics and Function","authors":"Yanjun Wang, Yanling Ding, Tana Wuren, Pengli Luo","doi":"10.1002/jbt.70291","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>To assess the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on mitochondrial damage and metabolic disorders induced by acute and chronic hypoxia in mouse kidneys.</p>\n </section>\n \n <section>\n \n <h3> Method</h3>\n \n <p>Comprehensive analyses were conducted, including histopathology, mitochondrial morphology analysis, biochemical assessments, transcriptomics and metabolomics.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The results revealed that hUC-MSCs significantly improved renal mitochondrial integrity and maintained mitochondrial dynamic balance under both acute and chronic hypoxia. This improvement was achieved by upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, which ultimately enhanced mitochondrial function. Furthermore, hUC-MSCs reprogrammed renal metabolic disorders, particularly improvements in urea and purine metabolic dysfunction, increased fatty acid oxidation and amelioration of lipid metabolic disorders.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>These findings suggest that hUC-MSCs could be part of a promising strategy for enhancing renal health and metabolic stability in individuals exposed to high altitudes or other hypoxic environments, highlighting their potential therapeutic value in addressing hypoxia-induced mitochondrial damage and renal metabolic disorders.</p>\n </section>\n </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70291","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

To assess the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on mitochondrial damage and metabolic disorders induced by acute and chronic hypoxia in mouse kidneys.

Method

Comprehensive analyses were conducted, including histopathology, mitochondrial morphology analysis, biochemical assessments, transcriptomics and metabolomics.

Results

The results revealed that hUC-MSCs significantly improved renal mitochondrial integrity and maintained mitochondrial dynamic balance under both acute and chronic hypoxia. This improvement was achieved by upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, which ultimately enhanced mitochondrial function. Furthermore, hUC-MSCs reprogrammed renal metabolic disorders, particularly improvements in urea and purine metabolic dysfunction, increased fatty acid oxidation and amelioration of lipid metabolic disorders.

Conclusion

These findings suggest that hUC-MSCs could be part of a promising strategy for enhancing renal health and metabolic stability in individuals exposed to high altitudes or other hypoxic environments, highlighting their potential therapeutic value in addressing hypoxia-induced mitochondrial damage and renal metabolic disorders.

查看原文本刊更多论文

间充质干细胞通过改善线粒体动力学和功能重编程小鼠肾脏缺氧诱导代谢紊乱

目的探讨人脐带间充质干细胞（hUC-MSCs）对小鼠急性和慢性缺氧所致肾脏线粒体损伤和代谢紊乱的影响。方法采用组织病理学、线粒体形态学、生化分析、转录组学和代谢组学等方法进行综合分析。结果hUC-MSCs在急慢性缺氧条件下均能显著改善肾线粒体完整性，维持线粒体动态平衡。这种改善是通过上调过氧化物酶体增殖物激活受体γ共激活因子-1 α的表达实现的，最终增强了线粒体功能。此外，hUC-MSCs对肾脏代谢紊乱进行了重编程，特别是改善尿素和嘌呤代谢功能障碍，增加脂肪酸氧化和改善脂质代谢紊乱。这些研究结果表明，hUC-MSCs可能是改善高海拔或其他低氧环境下个体肾脏健康和代谢稳定性的一种有希望的策略，突出了它们在解决缺氧诱导的线粒体损伤和肾脏代谢紊乱方面的潜在治疗价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.