过氧化物酶体增殖物激活受体介导的能量代谢重塑在肾疾病中的作用
Q591; 随着患病率的持续上升,肾疾病成为全球范围内严重的公共卫生问题,严重影响患者的生活质量.肾病的发病机制较为复杂为其防治带来了困难.研究发现,代谢稳态失衡通常会影响肾功能,进而引起肾病变.过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)作为内源性配体激活的转录因子,在调节代谢分子网络特别是氧化磷酸化、脂代谢和葡萄糖代谢中发挥重要作用.激活PPAR能够改善线粒体损伤,促进脂肪酸分解并减轻胰岛素抵抗,从而恢复肾的代谢功能和缓解肾的病变.尽管现已开发了多种激活PPAR的小分子药物,但该类药物在临床试验阶段出现不良反应...
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| Published in | 中国生物化学与分子生物学报 Vol. 41; no. 2; pp. 238 - 248 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
广东省医学免疫与分子诊断重点实验室,广东医科大学衰老研究所,广东医科大学生物化学与分子生物学研究所,广东医科大学医学技术学院,广东东莞 523808
01.02.2025
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1007-7626 |
| DOI | 10.13865/j.cnki.cjbmb.2024.11.1176 |
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| Abstract | Q591; 随着患病率的持续上升,肾疾病成为全球范围内严重的公共卫生问题,严重影响患者的生活质量.肾病的发病机制较为复杂为其防治带来了困难.研究发现,代谢稳态失衡通常会影响肾功能,进而引起肾病变.过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)作为内源性配体激活的转录因子,在调节代谢分子网络特别是氧化磷酸化、脂代谢和葡萄糖代谢中发挥重要作用.激活PPAR能够改善线粒体损伤,促进脂肪酸分解并减轻胰岛素抵抗,从而恢复肾的代谢功能和缓解肾的病变.尽管现已开发了多种激活PPAR的小分子药物,但该类药物在临床试验阶段出现不良反应.目前,临床治疗肾疾病仍缺乏安全有效的用药方案.精细解析PPAR家族调控肾的细胞能量代谢的分子机制,寻找和开发新的靶向PPAR及其调控的下游代谢途径的小分子药物,对于肾疾病的认知和诊治具有重要的意义.另一方面,明确不同肾疾病发生发展过程中的代谢变化,针对性地应用靶向PPAR的药物或策略对肾疾病的治疗也尤为重要.本文概述了 PPAR家族成员调控靶基因转录的方式及其在氧化磷酸化和糖脂代谢重塑中的作用,并归纳总结了 PPAR表达或活性的改变对急性、慢性肾病和年龄相关性肾疾病的影响,有望为肾疾病的防治提供新的思路和理论支撑. |
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| AbstractList | Q591; 随着患病率的持续上升,肾疾病成为全球范围内严重的公共卫生问题,严重影响患者的生活质量.肾病的发病机制较为复杂为其防治带来了困难.研究发现,代谢稳态失衡通常会影响肾功能,进而引起肾病变.过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)作为内源性配体激活的转录因子,在调节代谢分子网络特别是氧化磷酸化、脂代谢和葡萄糖代谢中发挥重要作用.激活PPAR能够改善线粒体损伤,促进脂肪酸分解并减轻胰岛素抵抗,从而恢复肾的代谢功能和缓解肾的病变.尽管现已开发了多种激活PPAR的小分子药物,但该类药物在临床试验阶段出现不良反应.目前,临床治疗肾疾病仍缺乏安全有效的用药方案.精细解析PPAR家族调控肾的细胞能量代谢的分子机制,寻找和开发新的靶向PPAR及其调控的下游代谢途径的小分子药物,对于肾疾病的认知和诊治具有重要的意义.另一方面,明确不同肾疾病发生发展过程中的代谢变化,针对性地应用靶向PPAR的药物或策略对肾疾病的治疗也尤为重要.本文概述了 PPAR家族成员调控靶基因转录的方式及其在氧化磷酸化和糖脂代谢重塑中的作用,并归纳总结了 PPAR表达或活性的改变对急性、慢性肾病和年龄相关性肾疾病的影响,有望为肾疾病的防治提供新的思路和理论支撑. |
| Abstract_FL | With the prevalence of kidney disease continues to rise,it has become a serious global public health issue that significantly impacts patients'quality of life.The complex pathogenesis of kidney disea-ses presents challenges for its prevention and treatment.Research has shown that imbalances in metabolic homeostasis often affect kidney function,leading to renal damage.Peroxisome proliferator-activated re-ceptors(PPARs),as transcription factors activated by endogenous ligands,play a crucial role in regula-ting metabolic molecular networks,particularly in oxidative phosphorylation,lipid metabolism,and glu-cose metabolism.Activating PPARs can improve mitochondrial damage,promote tatty acid breakdown,and alleviate insulin resistance,thereby restoring renal metabolic function and mitigating kidney damage.Although various small-molecule drugs that activate PPARs have been developed,adverse reactions have been observed during clinical trials.Currently,there is still a lack of safe and effective treatment options for kidney diseases.A detailed analysis of the molecular mechanisms by which the PPAR family regulates renal cell energy metabolism,as well as the search for and development of new small-molecule drugs tar-geting PPARs and their regulated downstream metabolic pathways,is of significant importance for under-standing and treating kidney diseases.On the other hand,clarifying the metabolic changes during the progression of different kidney diseases and applying targeted PPAR-based drugs or strategies for their treatment is particularly important.Here we summarize how PPAR family members regulate target gene transcription and their roles in the remodeling of oxidative phosphorylation and lipid/glucose metabolism,as well as the impact of changes in PPAR expression or activity on acute and chronic kidney diseases and age-related kidney conditions.This knowledge may provide new insights and theoretical support for the prevention and treatment of kidney diseases. |
| Author | 刘新光 杨萌 戴祺慧 |
| AuthorAffiliation | 广东省医学免疫与分子诊断重点实验室,广东医科大学衰老研究所,广东医科大学生物化学与分子生物学研究所,广东医科大学医学技术学院,广东东莞 523808 |
| AuthorAffiliation_xml | – name: 广东省医学免疫与分子诊断重点实验室,广东医科大学衰老研究所,广东医科大学生物化学与分子生物学研究所,广东医科大学医学技术学院,广东东莞 523808 |
| Author_FL | YANG Meng DAI Qi-Hui LIU Xin-Guang |
| Author_FL_xml | – sequence: 1 fullname: DAI Qi-Hui – sequence: 2 fullname: YANG Meng – sequence: 3 fullname: LIU Xin-Guang |
| Author_xml | – sequence: 1 fullname: 戴祺慧 – sequence: 2 fullname: 杨萌 – sequence: 3 fullname: 刘新光 |
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| Copyright | Copyright © Wanfang Data Co. Ltd. All Rights Reserved. |
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| DOI | 10.13865/j.cnki.cjbmb.2024.11.1176 |
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| DocumentTitle_FL | The Role of Peroxisome Proliferator-activated Receptor(PPAR)-mediated Energy Metabolism in Kidney Diseases |
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| Keywords | 过氧化物酶体增殖物激活受体 肾脏疾病 kidney peroxisome proliferator-activated receptor(PPAR) kidney diseases 肾 能量代谢 energy metabolism |
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| PublicationTitle | 中国生物化学与分子生物学报 |
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| Publisher | 广东省医学免疫与分子诊断重点实验室,广东医科大学衰老研究所,广东医科大学生物化学与分子生物学研究所,广东医科大学医学技术学院,广东东莞 523808 |
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| Title | 过氧化物酶体增殖物激活受体介导的能量代谢重塑在肾疾病中的作用 |
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