{
  "abstract": "Primary cilia are essential microtubule-based sensory organelles, and their dysfunction has been increasingly linked to metabolic stress. However, the underlying molecular mechanisms remain poorly understood. Herein, we reveal that ciliary defects in retinal photoreceptors and renal tubules exacerbate tissue damage during the progression of diabetic complications. Under hyperglycemic stress, protein arginine methyltransferase 1 (PRMT1) and histone deacetylase 6 (HDAC6) are significantly upregulated in both retinal and renal tissues. Genetic ablation of either enzyme effectively preserves ciliary architecture and restores organ function in diabetic mice. Mechanistically, PRMT1 localizes to the basal body, where it interacts with and methylates HDAC6 at arginine 16, consequently enhancing HDAC6 stability. In turn, HDAC6 mediates the deacetylation of PRMT1 at lysine 128, which elevates PRMT1 protein levels. This mutual modification crosstalk establishes a pathological positive feedback loop that stabilizes a pro-disassembly complex at the basal body, thereby potentiating ciliary impairment and expediting the progression of diabetic complications. Pharmacological inhibition of the PRMT1-HDAC6 loop significantly attenuates the pathological features of both diabetic retinopathy and nephropathy. Collectively, our findings uncover a reciprocal regulatory mechanism mediated by deacetylation and arginine methylation that drives cilium disassembly under hyperglycemic stress, providing promising therapeutic targets for the treatment of metabolic ciliopathies.\n\nPrimary cilium dysfunction contributes to diabetic complications, but the mechanisms linking hyperglycemia to cilium loss remain unclear. This study shows PRMT1-HDAC6 crosstalk drives cilium disassembly, identifying a therapeutic target for metabolic ciliopathies.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University, Jinan, China",
    "Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China",
    "Department of Genetics and Cell Biology, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China",
    "School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jie Ran"
    },
    {
      "affs": [
        1
      ],
      "name": "Changfeng Wei"
    },
    {
      "affs": [
        2
      ],
      "name": "Yang Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yufei Zhang"
    },
    {
      "name": "Guizhi Guo"
    },
    {
      "name": "Nan Ma"
    },
    {
      "name": "Long Yin"
    },
    {
      "name": "Hongjun Fan"
    },
    {
      "name": "Jingrui Li"
    },
    {
      "name": "Heng Guo"
    },
    {
      "name": "Renshuai Zhang"
    },
    {
      "name": "Runa Wang"
    },
    {
      "name": "Dengwen Li"
    },
    {
      "name": "Min Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a7hzzrrvrmt73.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3003975",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003975",
  "id": "a7hzzrrvrmt73",
  "issns": [
    "1545-7885"
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  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Genetic and Kidney Cyst Diseases"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Ocular system/Ocular anatomy/Retina"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cilia"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Neurons/Afferent neurons/Photoreceptors"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Sensory receptors/Photoreceptors"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Cellular neuroscience/Neurons/Afferent neurons/Photoreceptors"
    ],
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      "plos",
      "/Biology and life sciences/Neuroscience/Cognitive science/Cognitive psychology/Perception/Sensory perception/Sensory receptors/Photoreceptors"
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      "/Biology and life sciences/Neuroscience/Sensory perception/Sensory receptors/Photoreceptors"
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      "plos",
      "/Biology and life sciences/Psychology/Cognitive psychology/Perception/Sensory perception/Sensory receptors/Photoreceptors"
    ],
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      "/Medicine and health sciences/Anatomy/Ocular system/Ocular anatomy/Retina"
    ],
    [
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      "/Medicine and health sciences/Endocrinology/Endocrine disorders/Diabetes mellitus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Metabolic disorders/Diabetes mellitus"
    ],
    [
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      "/Physical sciences/Chemistry/Chemical reactions/Methylation"
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      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models"
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      "plos",
      "/Research and analysis methods/Model organisms/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
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      "/Research and analysis methods/Precipitation techniques/Immunoprecipitation"
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    [
      "plos",
      "/Social sciences/Psychology/Cognitive psychology/Perception/Sensory perception/Sensory receptors/Photoreceptors"
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  "openalex": "W7207834048",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003975&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/a7hzzrrvrmt73.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.pbio.3003975",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003975"
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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      "field": "biology",
      "origin": "plos:neuroscience",
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism",
  "title_text": "Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/a7hzzrrvrmt73",
  "venue": "PLOS Biology",
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