ArticleFrontiers in physiology2022
CCL5 Suppresses Klotho Expression
Article in Frontiers in physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Article
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Sustained Accumulation of Molecular Clock Suppressors Period 1 and Period 2 Promotes C2C12 Myotube Atrophy Through an Autocrine-Mediated Mechanism With Relevance to Androgen Deprivation-Induced Limb Muscle Mass Loss.Function (Oxford, England) · 2025Article
- DNMT3B aggravated renal fibrosis in diabetic kidney disease via activating Wnt/β-catenin signaling pathway.Scientific reports · 2025Article
- Therapeutic potential of voltage-dependent potassium channel subtype 1.3 blockade in alleviating macrophage-related renal inflammation and fibrogenesis.Cell death discovery · 2025Article
- A PDE1 inhibitor, vinpocetine, ameliorates epithelial-mesenchymal transition and renal fibrosis in adenine-induced chronic kidney injury in rats by targeting the DNMT1/Klotho/β-catenin/Snail 1 and MMP-7 pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- Article
- Epigenetic roles in clonal hematopoiesis and aging kidney-related chronic kidney disease.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Enhanced inflammation and reduced Klotho are common features in chronic kidney disease (CKD). Inflammation induces DNA hypermethylation. This study assessed the performance of inflammatory marker C-C motif chemokine 5 (CCL5) in epigenetic regulation of Klotho expression. Methods: Fifty CKD patients and 25 matched controls were enrolled, and serum CCL5 level, sKlotho level, and DNA methylation were evaluated in these subjects. A renal interstitial fibrosis (RIF) model with CKD was induced in mice Results: CCL5 upregulation concomitant with Klotho downregulation in serum and global DNA methylation in PBLs were observed in CKD samples. UUO contributed to severe renal interstitial fibrosis and enhanced expressions of fibrotic markers. Moreover, UUO increased the CCL5 level, induced Klotho promoter methylation, suppressed Klotho level, activated p-STAT3 signaling, and upregulated DNMT1 level. A similar observation was made in HK-2 cells treated with CCL5. More importantly, 5-Aza inhibited UUO-induced Klotho hypermethylation, reversed Klotho, downregulated p-STAT3 expressions, and ameliorated RIF Conclusion: The CCL5/p-STAT3/DNMT1 axis is implicated in epigenetic regulation of Klotho expression in CKD. This study provides novel therapeutic possibilities for reversal of Klotho suppression by CKD.
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