ArticleCell death & disease2023
Klotho prevents transforming growth factor-β2-induced senescent-like morphological changes in the retinal pigment epithelium.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Preformed fibrils of α-synuclein rapidly activate LRRK2 on early endosomes, driving Rab5 phosphorylation and disrupting endolysosomal and synaptic function.NPJ Parkinson's disease · 2026Article
- β-Klotho inhibited the epithelial-mesenchymal transition of liver sinusoidal endothelial cells to alleviate schistosomiasis liver fibrosis.PLoS pathogens · 2026Article
- Serum Klotho Levels and Major Age-Related Ocular Disorders: A Cross-Sectional and Genetic Association Study.Translational vision science & technology · 2026Article
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration.Frontiers in cell and developmental biology · 2026Article
- Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression.Biomolecules · 2025Review
- Hallmarks of aging in age-related macular degeneration and age-related neurological disorders: novel insights into common mechanisms and clinical relevance.Eye (London, England) · 2025Review
- Klotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.International journal of molecular medicine · 2025Article
- Klotho Protein: A Multifaceted Guardian of Healthy Aging and Its Therapeutic Potential.International journal of nanomedicine · 2025Review
- IGF-1 Signaling Modulates Oxidative Metabolism and Stress Resistance in ARPE-19 Cells Through PKM2 Function.International journal of molecular sciences · 2024Article
- Klotho relieves HInternational ophthalmology · 2024Article
- Review
- Epithelial-mesenchymal Transition (EMT) and the Effect of Atorvastatin on it in ARPE-19 cells.Cell biochemistry and biophysics · 2024Article
- Article
- Review
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Degenerative changes of the retinal pigment epithelium (RPE) triggered by transforming growth factor-β2 (TGF-β2) and oxidative stress play a critical role in the progression of age-related macular degeneration (AMD). The expression of α-klotho, an antiaging protein, declines with age, increasing the risk factors for age-related diseases. Here, we investigated the protective effects of soluble α-klotho on TGF-β2-induced RPE degeneration. The morphological changes induced by TGF-β2, including epithelial-mesenchymal transition (EMT), were attenuated in the mouse RPE by the intravitreal injection (IVT) of α-klotho. In ARPE19 cells, EMT and morphological alterations by TGF-β2 were attenuated by co-incubation with α-klotho. TGF-β2 decreased miR-200a accompanied by zinc finger e-box binding homeobox1 (ZEB1) upregulation and EMT, all of which were prevented by α-klotho co-treatment. Inhibitor of miR-200a mimicked TGF-β2-induced morphological changes, which were recovered by ZEP1 silencing, but not by α-klotho, implying the upstream regulation of α-klotho on miR-200a-ZEP1-EMT axis. α-Klotho inhibited receptor binding of TGF-β2, Smad2/3 phosphorylation, extracellular signal-regulated protein kinase 1/2 (ERK1/2)-a mechanistic target of rapamycin (mTOR) activation and oxidative stress via NADPH oxidase 4 (NOX4) upregulation. Furthermore, α-klotho recovered the TGF-β2-induced mitochondrial activation and superoxide generation. Interestingly, TGF-β2 upregulated α-klotho expression in the RPE cells, and genetic suppression of endogenous α-klotho aggravated TGF-β2-induced oxidative stress and EMT. Lastly, α-klotho abrogated senescence-associated signaling molecules and phenotypes induced by long-term incubation with TGF-β2. Hence, our findings indicate that the antiaging α-klotho plays a protective role against EMT and degeneration of the RPE, demonstrating the therapeutic potential for age-related retinal diseases, including the dry type of AMD.
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