ArticleCell communication and signaling : CCS2024
α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- HECTD1 Directs HIF-1α to Facilitate Intestinal Inflammation and Carcinogenesis via Promoting Th17 Differentiation and Glycolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Characterization of Umbilical Cord Mesenchymal Stromal Cells Overexpressing Klotho and In Vitro Anti-Aging Efficacy of Their Derived Extracellular Vesicles.International journal of molecular sciences · 2026Article
- Age-Associated Senescence of Decidual Macrophages: A Key Mediator of Adverse Pregnancy Outcomes in Advanced Maternal Age.Aging cell · 2026Article
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Integrin β3 Promotes Retinal Neovascularization via Endoplasmic Reticulum Stress-Mediated Endothelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
- LIN28A blocks the EndMT process of high glucose-induced HRMECs by stabilizing SIRT6 mRNA.Journal of diabetes investigation · 2026Article
- Serum Klotho Levels and Major Age-Related Ocular Disorders: A Cross-Sectional and Genetic Association Study.Translational vision science & technology · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Dual immune armies in glaucoma: microglia and monocyte-derived macrophages.Frontiers in immunology · 2026Review
- Employing the Role of SLC40A1-Mediated Microglia Inflammatory Response in Diabetic Retinopathy Based on Single-Cell Transcriptomics Technology.ASN neuro · 2026Article
- Deciphering the therapeutic mechanism of kaempferol in diabetic retinopathy via the P21/Thioredoxin axis.Molecular and cellular biochemistry · 2026Article
- Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy.Nature communications · 2025Article
- Ginkgo Biloba extract attenuates diabetic retinopathy progression by modulating TP53 ubiquitination in a rat model.Molecular biology reports · 2025Article
- Immunoinflammation and post-translational modifications in the aging process.Journal of translational medicine · 2025Review
- Lipid metabolism disorder promoting retinal structural and functional damage in ApoEActa neuropathologica communications · 2025Article
- Macrophage Depletion Alleviates Immunosenescence in Diabetic Kidney by Modulating GDF-15 and Klotho.International journal of molecular sciences · 2025Article
- CD44, ACAN, PLVAP, and HBEGF Emerged as Potential Biomarkers in Diabetic Retinopathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Klotho in diabetes mellitus: research progress and clinical implications.Frontiers in endocrinology · 2025Review
- The relationship of serum klotho levels and triglyceride glucose index-related indicators.Lipids in health and disease · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) and a significant cause of acquired blindness in the working-age population worldwide. Aging is considered as an important risk factor for DR development. Macrophages in aged mice bear typical M2 marker proteins but simultaneously express a pro-inflammatory factor profile. This may explain why the level of intraocular inflammation does not decrease during proliferative diabetic retinopathy (PDR) despite the occurrence of neovascularization and fibrosis (M2 activation). α-Klotho (KL) was originally discovered as a soluble anti-aging factor, which is mainly expressed in kidney tubular epithelium, choroid plexus in the brain and secreted in the blood. However, the role of KL in DR pathophysiology has not been previously reported.
methodsType 1 (streptozotocin [STZ]-induced) and type 2 (a high-fat diet along with a low dose of STZ) diabetic mouse models were established and injected with or without KL adenovirus via the tail vein for 12 weeks. Vldlr
resultsSerum, aqueous humor, and vitreous humor KL levels were lower in patients with PDR than in those with cataracts. KL relieved the retinal structure damage, improved retina function, and inhibited retinal senescence in diabetic mice. KL administration attenuated the neovascular lesions in VLDLR
conclusionsMacrophage aging is involved in DM-induced retinopathy. KL alleviates DM-induced retinal macrophage senescence by downregulating HECTD1 and decreasing IRS1 ubiquitination and degradation. Meanwhile, KL administration attenuated the neovascular lesions by altering the activation state of macrophages and decreasing the expression of VEGFA and FGF2.
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