{
    "abstract": "Set7 knockout improves diabetic glomerular structure and function and prevents diabetes-induced endothelial\u2013mesenchymal transition (EDMT) by regulating Igfbp5. Set7 knockdown prevents, and (R)-PFI-2 hydrochloride reverses, diabetes-induced EDMT by regulating insulin growth factor binding protein 5. Set7 regulates the phenotypic EDMT switch, and inhibiting the methyltransferase attenuates glomerular injury in diabetic kidney disease.\nHyperglycemia influences the development of glomerular endothelial cell damage, and nowhere is this more evident than in the progression of diabetic kidney disease (DKD). While the Set7 lysine methyltransferase is a known hyperglycemic sensor, its role in endothelial cell function in the context of DKD remains poorly understood.\nSingle-cell transcriptomics was used to investigate Set7 regulation in a mouse model of DKD, followed by validation of findings using pharmacological and short hairpin RNA inhibition inhibition of Set7.\nSet7 knockout (Set7KO) improved glomerular structure and albuminuria in a mouse model of diabetes. Analysis of single-cell RNA-sequencing data showed dynamic transcriptional changes in diabetic renal cells. Set7KO controls phenotype switching of glomerular endothelial cell populations by transcriptional regulation of the insulin growth factor binding protein 5 (IGFBP5). Chromatin immunoprecipitation assays confirmed that the expression of the \nSet7 regulates the phenotypic endothelial\u2013mesenchymal transition switch and suggests that targeting the lysine methyltransferase could protect glomerular cell injury in DKD.\nThis article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_04_25_ASN0000000000000345.mp3",
    "authors": [
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Scott",
            "initials": "S",
            "lastname": "Maxwell"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Jun",
            "initials": "J",
            "lastname": "Okabe"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.\nDepartment of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.",
            "firstname": "Harikrishnan",
            "initials": "H",
            "lastname": "Kaipananickal"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Hanah",
            "initials": "H",
            "lastname": "Rodriguez"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Ishant",
            "initials": "I",
            "lastname": "Khurana"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Keith",
            "initials": "K",
            "lastname": "Al-Hasani"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Bryna S M",
            "initials": "BSM",
            "lastname": "Chow"
        },
        {
            "affiliation": "School of Science, STEM College, RMIT University, Melbourne, Victoria, Australia.",
            "firstname": "Eleni",
            "initials": "E",
            "lastname": "Pitsillou"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.\nSchool of Science, STEM College, RMIT University, Melbourne, Victoria, Australia.",
            "firstname": "Tom C",
            "initials": "TC",
            "lastname": "Karagiannis"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.\nGerman Diabetes Centre, Institute for Clinical Diabetology, Research Group Diabetic Nephropathy, Heinrich Heine University, Duesseldorf, Germany.",
            "firstname": "Karin",
            "initials": "K",
            "lastname": "Jandeleit-Dahm"
        },
        {
            "affiliation": "Department of Medicine and Therapeutics, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nHong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.",
            "firstname": "Ronald C W",
            "initials": "RCW",
            "lastname": "Ma"
        },
        {
            "affiliation": "Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nSchool of Biomedical Sciences, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.",
            "firstname": "Yu",
            "initials": "Y",
            "lastname": "Huang"
        },
        {
            "affiliation": "Department of Medicine and Therapeutics, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nHong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nLi Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.",
            "firstname": "Juliana C N",
            "initials": "JCN",
            "lastname": "Chan"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.",
            "firstname": "Mark E",
            "initials": "ME",
            "lastname": "Cooper"
        },
        {
            "affiliation": "Epigenetics in Human Health and Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.\nEpigenetics in Human Health and Disease Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.\nDepartment of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.\nDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nHong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nSchool of Biomedical Sciences, The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.\nDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.\nUniversity College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science, Copenhagen, Denmark.",
            "firstname": "Assam",
            "initials": "A",
            "lastname": "El-Osta"
        }
    ],
    "conclusions": null,
    "copyrights": null,
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    "journal": "Journal of the American Society of Nephrology : JASN",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-04-17",
    "pubmed_id": "38630537\n24892707\n21045787\n25411387\n30607032\n18987304\n19729486\n30864875\n32373613\n18809715\n19208907\n22403242\n18650421\n19237535\n25472959\n20930066\n27292644\n29222115\n26045091\n32448511\n33848540\n26000488\n31178118\n16557232\n27439711\n24850797\n15284298\n25136132\n24452638\n31836710\n32059779\n26025657\n33867398\n7556948\n9032105\n32320649\n20595396\n35913792\n28347704\n26842599\n17660828\n17979880\n15031262\n32194505\n30510133\n31506348\n35418167\n19864299\n33035436\n15001525\n32173197",
    "results": "Set7 knockout (Set7KO) improved glomerular structure and albuminuria in a mouse model of diabetes. Analysis of single-cell RNA-sequencing data showed dynamic transcriptional changes in diabetic renal cells. Set7KO controls phenotype switching of glomerular endothelial cell populations by transcriptional regulation of the insulin growth factor binding protein 5 (IGFBP5). Chromatin immunoprecipitation assays confirmed that the expression of the ",
    "title": "Set7 Methyltransferase and Phenotypic Switch in Diabetic Glomerular Endothelial Cells.",
    "xml": "<Element 'PubmedArticle' at 0x788505c325c0>"
}