ArticleKidney international2015
Mammalian target of rapamycin signaling inhibition ameliorates vascular calcification via Klotho upregulation.
Article in Kidney international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
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Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Correlation Between Soluble Klotho and Vascular Calcification in Chronic Kidney Disease: A Meta-Analysis and Systematic Review.Frontiers in physiology · 2021Pooled it
- The Protective Effects of the Autophagic and Lysosomal Machinery in Vascular and Valvular Calcification: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Use of Calcium Modification in Percutaneous Coronary Intervention: A Comprehensive Review.Journal of clinical medicine · 2025Review
- [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
- Rapamycin reduces mineral density and promotes beneficial vascular remodeling in a murine model of severe medial arterial calcification.American journal of physiology. Heart and circulatory physiology · 2025Article
- Rapamycin Reduces Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification.bioRxiv : the preprint server for biology · 2025Article
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- Identification of potential biomarkers for diabetic nephropathy via UPLC-MS/MS-based metabolomics.Frontiers in endocrinology · 2025Article
- Article
- α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages.Cell communication and signaling : CCS · 2024Article
- The interaction between klotho protein and epigenetic alteration in diabetes and treatment options.Journal of diabetes and metabolic disorders · 2024Review
- Similarities and Differences of Vascular Calcification in Diabetes and Chronic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients.The Journal of clinical investigation · 2023Article
- Rapamycin treatment increases survival, autophagy biomarkers and expression of the anti-aging klotho protein in elderly mice.Pharmacology research & perspectives · 2023Article
- The Anti-Aging Hormone Klotho Promotes Retinal Pigment Epithelium Cell Viability and Metabolism by Activating the AMPK/PGC-1α Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Review
- Rapamycin downregulates α-klotho in the kidneys of female rats with normal and reduced renal function.PloS one · 2023Article
- Klotho inversely relates with carotid intima- media thickness in atherosclerotic patients with normal renal function (eGFR ≥60 mL/min/1.73mFrontiers in endocrinology · 2023Article
- Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.Frontiers in endocrinology · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular calcification (VC) is a major risk factor for cardiovascular mortality in chronic renal failure (CRF) patients, but the pathogenesis remains partially unknown and effective therapeutic targets should be urgently explored. Here we pursued the therapeutic role of rapamycin in CRF-related VC. Mammalian target of rapamycin (mTOR) signal was activated in the aortic wall of CRF rats. As expected, oral rapamycin administration significantly reduced VC by inhibiting mTOR in rats with CRF. Further in vitro results showed that activation of mTOR by both pharmacological agent and genetic method promoted, while inhibition of mTOR reduced, inorganic phosphate-induced vascular smooth muscle cell (VSMC) calcification and chondrogenic/osteogenic gene expression, which were independent of autophagy and apoptosis. Interestingly, the expression of Klotho, an antiaging gene that suppresses VC, was reduced in calcified vasculature, whereas rapamycin reversed membrane and secreted Klotho decline through mTOR inhibition. When mTOR signaling was enhanced by either mTOR overexpression or deletion of tuberous sclerosis 1, Klotho mRNA was further decreased in phosphate-treated VSMCs, suggesting a vital association between mTOR signaling and Klotho expression. More importantly, rapamycin failed to reduce VC in the absence of Klotho by using either siRNA knockdown of Klotho or Klotho knockout mice. Thus, Klotho has a critical role in mediating the observed decrease in calcification by rapamycin in vitro and in vivo.
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Registered trials
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