{"title":"通过调节肉碱棕榈酰基转移酶-1A诱导的糖尿病肾病脂质代谢，肝脏再生增强基因敲除可加重肾小管铁变态反应和巨噬细胞活化。","authors":"Yuanyuan Zhang, Zheng Zhang, Lili Huang, Chunxia Wang, Pengfei Yang, Ling Zhang, Xiaohui Liao","doi":"10.1111/apha.14159","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>Ferroptosis is a novel type of programmed cell death that performs a critical function in diabetic nephropathy (DN). Augmenter of liver regeneration (ALR) exists in the inner membrane of mitochondria, and inhibits inflammation, apoptosis, and oxidative stress in acute kidney injury; however, its role in DN remains unexplored. Here, we aimed to identify the role of ALR in ferroptosis induction and macrophage activation in DN.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The expression of ALR was examined in DN patients, db/db DN mice, and HK-2 cells treated with high glucose (HG). The effects of ALR on ferroptosis and macrophage activation were investigated with ALR conditional knockout, lentivirus transfection, transmission electron microscopy, qRT-PCR and western blotting assay. Mass spectrometry and rescue experiments were conducted to determine the mechanism of ALR.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>ALR expression was reduced in the kidney tissues of DN patients and mice, serum of DN patients, and HG-HK-2 cells. Moreover, the inhibition of ALR promoted ferroptosis, macrophage activation, and DN progression. Mechanistically, ALR can directly bind to carnitine palmitoyltransferase-1A (CPT1A), the key rate-limiting enzyme of fatty acid oxidation (FAO), and inhibit the expression of CPT1A to regulate lipid metabolism involving FAO and lipid droplet-mitochondrial coupling in DN.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Taken together, our findings revealed a crucial protective role of ALR in ferroptosis induction and macrophage activation in DN and identified it as an alternative diagnostic marker and therapeutic target for DN.</p>\n </section>\n </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14159","citationCount":"0","resultStr":"{\"title\":\"Augmenter of liver regeneration knockout aggravates tubular ferroptosis and macrophage activation by regulating carnitine palmitoyltransferase-1A-induced lipid metabolism in diabetic nephropathy\",\"authors\":\"Yuanyuan Zhang, Zheng Zhang, Lili Huang, Chunxia Wang, Pengfei Yang, Ling Zhang, Xiaohui Liao\",\"doi\":\"10.1111/apha.14159\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>Ferroptosis is a novel type of programmed cell death that performs a critical function in diabetic nephropathy (DN). Augmenter of liver regeneration (ALR) exists in the inner membrane of mitochondria, and inhibits inflammation, apoptosis, and oxidative stress in acute kidney injury; however, its role in DN remains unexplored. Here, we aimed to identify the role of ALR in ferroptosis induction and macrophage activation in DN.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The expression of ALR was examined in DN patients, db/db DN mice, and HK-2 cells treated with high glucose (HG). The effects of ALR on ferroptosis and macrophage activation were investigated with ALR conditional knockout, lentivirus transfection, transmission electron microscopy, qRT-PCR and western blotting assay. Mass spectrometry and rescue experiments were conducted to determine the mechanism of ALR.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>ALR expression was reduced in the kidney tissues of DN patients and mice, serum of DN patients, and HG-HK-2 cells. Moreover, the inhibition of ALR promoted ferroptosis, macrophage activation, and DN progression. Mechanistically, ALR can directly bind to carnitine palmitoyltransferase-1A (CPT1A), the key rate-limiting enzyme of fatty acid oxidation (FAO), and inhibit the expression of CPT1A to regulate lipid metabolism involving FAO and lipid droplet-mitochondrial coupling in DN.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Taken together, our findings revealed a crucial protective role of ALR in ferroptosis induction and macrophage activation in DN and identified it as an alternative diagnostic marker and therapeutic target for DN.</p>\\n </section>\\n </div>\",\"PeriodicalId\":107,\"journal\":{\"name\":\"Acta Physiologica\",\"volume\":\"240 7\",\"pages\":\"\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14159\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Physiologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/apha.14159\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Physiologica","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/apha.14159","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Augmenter of liver regeneration knockout aggravates tubular ferroptosis and macrophage activation by regulating carnitine palmitoyltransferase-1A-induced lipid metabolism in diabetic nephropathy
Aim
Ferroptosis is a novel type of programmed cell death that performs a critical function in diabetic nephropathy (DN). Augmenter of liver regeneration (ALR) exists in the inner membrane of mitochondria, and inhibits inflammation, apoptosis, and oxidative stress in acute kidney injury; however, its role in DN remains unexplored. Here, we aimed to identify the role of ALR in ferroptosis induction and macrophage activation in DN.
Methods
The expression of ALR was examined in DN patients, db/db DN mice, and HK-2 cells treated with high glucose (HG). The effects of ALR on ferroptosis and macrophage activation were investigated with ALR conditional knockout, lentivirus transfection, transmission electron microscopy, qRT-PCR and western blotting assay. Mass spectrometry and rescue experiments were conducted to determine the mechanism of ALR.
Results
ALR expression was reduced in the kidney tissues of DN patients and mice, serum of DN patients, and HG-HK-2 cells. Moreover, the inhibition of ALR promoted ferroptosis, macrophage activation, and DN progression. Mechanistically, ALR can directly bind to carnitine palmitoyltransferase-1A (CPT1A), the key rate-limiting enzyme of fatty acid oxidation (FAO), and inhibit the expression of CPT1A to regulate lipid metabolism involving FAO and lipid droplet-mitochondrial coupling in DN.
Conclusion
Taken together, our findings revealed a crucial protective role of ALR in ferroptosis induction and macrophage activation in DN and identified it as an alternative diagnostic marker and therapeutic target for DN.
期刊介绍：
Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.
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