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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.<\/jats:p>","DOI":"10.1371\/journal.pbio.3003975","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:31:23Z","timestamp":1788456683000},"page":"e3003975","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperglycemic stress aggravates diabetic retinopathy and nephropathy by promoting cilium disassembly via a deacetylation- and methylation-mediated regulatory mechanism"],"prefix":"10.1371","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-7126","authenticated-orcid":true,"given":"Jie","family":"Ran","sequence":"first","affiliation":[{"name":"College of Life Sciences, Shandong Normal 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