Shuai Zheng, Yi Zeng, Liqing Chu, Taiyang Gong, Sihong Li, Min Yang
{"title":"糖尿病肾病中肾组织衍生的外泌体 miRNA-34a 通过促进 M1 型巨噬细胞极化诱导肾小管细胞纤维化","authors":"Shuai Zheng, Yi Zeng, Liqing Chu, Taiyang Gong, Sihong Li, Min Yang","doi":"10.1049/2024/5702517","DOIUrl":null,"url":null,"abstract":"<div>\n <p><i>Background</i>. Diabetic nephropathy (DN) is the leading cause of chronic kidney disease, and the activation and infiltration of phagocytes are critical steps of DN. This study aimed to explore the mechanism of exosomes in macrophages and diabetes nephropathy and the role of miRNA-34a, which might provide a new path for treating DN. <i>Materials and Methods</i>. The DN model was established, and the success of the model establishment was confirmed by detecting general indicators, HE staining, and immunohistochemistry. Electron microscopy and NanoSight Tracking Analysis (NTA) were used to see the morphology and size of exosomes. MiRNA-34a inhibitor, miRNA-34a mimics, pc-<i>PPARGC1A</i>, and controls were transfected in macrophages with or without kidney exosomal. A dual-luciferase reporter gene experiment verifies the targeting relationship between miRNA-34a and <i>PPARGC1A</i>. After exosomal culture, macrophages are co-cultured with normal renal tubular cells to detect renal tubular cell fibrosis. Q-PCR and western blot were undertaken to detect related RNA and proteins. <i>Results</i>. An animal model of diabetic nephropathy was successfully constructed. Macrophages could phagocytose exosomes. After ingesting model exosomes, M1 macrophages were activated, while M2 macrophages were weakened, indicating the model mice’s kidney exosomes caused the polarization. MiRNA-34a inhibitor increased <i>PPARGC1A</i> expression. MiRNA-34a expressed higher in diabetic nephropathy Model-Exo. MiRNA-34a negatively regulated <i>PPARGC1A</i>. <i>PPARGC1A</i> rescued macrophage polarization and renal tubular cell fibrosis. <i>Conclusion</i>. Exosomal miRNA-34a of tubular epithelial cells promoted M1 macrophage activation in diabetic nephropathy via negatively regulating <i>PPARGC1A</i> expression, which may provide a new direction for further exploration of DN treatment.</p>\n </div>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"2024 1","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1049/2024/5702517","citationCount":"0","resultStr":"{\"title\":\"Renal Tissue-Derived Exosomal miRNA-34a in Diabetic Nephropathy Induces Renal Tubular Cell Fibrosis by Promoting the Polarization of M1 Macrophages\",\"authors\":\"Shuai Zheng, Yi Zeng, Liqing Chu, Taiyang Gong, Sihong Li, Min Yang\",\"doi\":\"10.1049/2024/5702517\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n <p><i>Background</i>. Diabetic nephropathy (DN) is the leading cause of chronic kidney disease, and the activation and infiltration of phagocytes are critical steps of DN. This study aimed to explore the mechanism of exosomes in macrophages and diabetes nephropathy and the role of miRNA-34a, which might provide a new path for treating DN. <i>Materials and Methods</i>. The DN model was established, and the success of the model establishment was confirmed by detecting general indicators, HE staining, and immunohistochemistry. Electron microscopy and NanoSight Tracking Analysis (NTA) were used to see the morphology and size of exosomes. MiRNA-34a inhibitor, miRNA-34a mimics, pc-<i>PPARGC1A</i>, and controls were transfected in macrophages with or without kidney exosomal. A dual-luciferase reporter gene experiment verifies the targeting relationship between miRNA-34a and <i>PPARGC1A</i>. After exosomal culture, macrophages are co-cultured with normal renal tubular cells to detect renal tubular cell fibrosis. Q-PCR and western blot were undertaken to detect related RNA and proteins. <i>Results</i>. An animal model of diabetic nephropathy was successfully constructed. Macrophages could phagocytose exosomes. After ingesting model exosomes, M1 macrophages were activated, while M2 macrophages were weakened, indicating the model mice’s kidney exosomes caused the polarization. MiRNA-34a inhibitor increased <i>PPARGC1A</i> expression. MiRNA-34a expressed higher in diabetic nephropathy Model-Exo. MiRNA-34a negatively regulated <i>PPARGC1A</i>. <i>PPARGC1A</i> rescued macrophage polarization and renal tubular cell fibrosis. <i>Conclusion</i>. Exosomal miRNA-34a of tubular epithelial cells promoted M1 macrophage activation in diabetic nephropathy via negatively regulating <i>PPARGC1A</i> expression, which may provide a new direction for further exploration of DN treatment.</p>\\n </div>\",\"PeriodicalId\":13393,\"journal\":{\"name\":\"IET nanobiotechnology\",\"volume\":\"2024 1\",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-04-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1049/2024/5702517\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"IET nanobiotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1049/2024/5702517\",\"RegionNum\":4,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"IET nanobiotechnology","FirstCategoryId":"5","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1049/2024/5702517","RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Renal Tissue-Derived Exosomal miRNA-34a in Diabetic Nephropathy Induces Renal Tubular Cell Fibrosis by Promoting the Polarization of M1 Macrophages
Background. Diabetic nephropathy (DN) is the leading cause of chronic kidney disease, and the activation and infiltration of phagocytes are critical steps of DN. This study aimed to explore the mechanism of exosomes in macrophages and diabetes nephropathy and the role of miRNA-34a, which might provide a new path for treating DN. Materials and Methods. The DN model was established, and the success of the model establishment was confirmed by detecting general indicators, HE staining, and immunohistochemistry. Electron microscopy and NanoSight Tracking Analysis (NTA) were used to see the morphology and size of exosomes. MiRNA-34a inhibitor, miRNA-34a mimics, pc-PPARGC1A, and controls were transfected in macrophages with or without kidney exosomal. A dual-luciferase reporter gene experiment verifies the targeting relationship between miRNA-34a and PPARGC1A. After exosomal culture, macrophages are co-cultured with normal renal tubular cells to detect renal tubular cell fibrosis. Q-PCR and western blot were undertaken to detect related RNA and proteins. Results. An animal model of diabetic nephropathy was successfully constructed. Macrophages could phagocytose exosomes. After ingesting model exosomes, M1 macrophages were activated, while M2 macrophages were weakened, indicating the model mice’s kidney exosomes caused the polarization. MiRNA-34a inhibitor increased PPARGC1A expression. MiRNA-34a expressed higher in diabetic nephropathy Model-Exo. MiRNA-34a negatively regulated PPARGC1A. PPARGC1A rescued macrophage polarization and renal tubular cell fibrosis. Conclusion. Exosomal miRNA-34a of tubular epithelial cells promoted M1 macrophage activation in diabetic nephropathy via negatively regulating PPARGC1A expression, which may provide a new direction for further exploration of DN treatment.
期刊介绍：
Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level.
Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries.
IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to:
Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques)
Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology
Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools)
Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles)
Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance
Techniques for probing cell physiology, cell adhesion sites and cell-cell communication
Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology
Societal issues such as health and the environment
Special issues. Call for papers:
Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf
Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf
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