ArticleScientific reports2017
Klotho preservation via histone deacetylase inhibition attenuates chronic kidney disease-associated bone injury in mice.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Reversion of aortic valve cells calcification by activation of Notch signalling via histone acetylation induction.Signal transduction and targeted therapy · 2025Article
- Serum alpha-klotho levels associate with bone mineral density in chronic kidney disease patients from NHANES 2011 to 2016.Scientific reports · 2025Article
- Long-term effects of s-KL treatment in wild-type mice: Enhancing longevity, physical well-being, and neurological resilience.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach.Chinese medical journal · 2025Article
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
- Kidney Aging and Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- Article
- New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.Frontiers in immunology · 2024Review
- PKC regulates αKlotho gene expression in MDCK and NRK-52E cells.Pflugers Archiv : European journal of physiology · 2024Article
- Inflammation and gut dysbiosis as drivers of CKD-MBD.Nature reviews. Nephrology · 2023Review
- Mouse Models of Mineral Bone Disorders Associated with Chronic Kidney Disease.International journal of molecular sciences · 2023Review
- AAV-mediated expression of secreted and transmembrane αKlotho isoforms rescues relevant aging hallmarks in senescent SAMP8 mice.Aging cell · 2022Article
- [Cultivation and characterization of primary human parathyroid cells from patients with severe secondary hyperparathyroidism].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Class IIa histone deacetylase inhibition ameliorates acute kidney injury by suppressing renal tubular cell apoptosis and enhancing autophagy and proliferation.Frontiers in pharmacology · 2022Article
- Pharmacological and Genetic Inhibition of HDAC4 Alleviates Renal Injury and Fibrosis in Mice.Frontiers in pharmacology · 2022Article
- Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease.Pharmaceutics · 2021Review
- Epigenetic modifications of Klotho expression in kidney diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Histone Acetylation in the Epigenetic Regulation of Bone Metabolism and Related Diseases.Stem cells international · 2021Review
- Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").Frontiers in endocrinology · 2021Review
- Identification of histone deacetylase 8 as a novel therapeutic target for renal fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone loss and increased fracture are the devastating outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD) resulting from Klotho deficit-related mineral disturbance and hyperparathyroidism. Because Klotho down-regulation after renal injury is presumably affected by aberrant histone deacetylase (HDAC) activities, here we assess whether HDAC inhibition prevents Klotho loss and attenuates the CKD-associated bone complication in a mouse model of CKD-MBD. Mice fed adenine-containing diet developed the expected renal damage, a substantial Klotho loss and the deregulated key factors causally affecting bone remodeling, which were accompanied by a marked reduction of bone mineral density. Intriguingly, administration of a potent HDAC inhibitor trichostatin A (TSA) impressively alleviated the Klotho deficit and the observed alterations of serum, kidney and bone. TSA prevented Klotho loss by increasing the promoter-associated histone acetylation, therefore increasing Klotho transcription. More importantly the mice lacking Klotho by siRNA interference largely abolished the TSA protections against the serum and renal abnormalities, and the deranged bone micro-architectures. Thus, our study identified Klotho loss as a key event linking HDAC deregulation to the renal and bone injuries in CKD-MBD mice and demonstrated the therapeutic potentials of endogenous Klotho restoration by HDAC inhibition in treating CKD and the associated extrarenal complications.
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