ArticleCell death & disease2017
Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Pharmaceutical Strategies for Translating Klotho-Based Therapeutics: From Biologic Developability to Advanced Delivery Systems.Pharmaceutics · 2026Review
- Bone transcriptomics reveals that juzentaihoto remodels and activates multiple pathways in Klotho-deficient mice.Bone reports · 2026Article
- Hyperbranched poly(β-amino ester)s-mediated delivery of engineered Klotho mRNA rescues senescence and restores cellular homeostasis in aged and Klotho deficient iMSCs.Drug delivery and translational research · 2026Article
- [Effect of pioglitazone on periodontitis-related renal injury in mice and its relationship with Klotho].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026Article
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Klotho in aging and diseases: molecular features, expressions, and functional implications.Molecular and cellular biochemistry · 2026Review
- Review
- Serum α-Klotho and SIRT1 - Relationship with graft function, inflammation and hospitalization rates in kidney transplant recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2026Observational
- Progress and prospect of minicircle as a minimized non-viral DNA vector in gene therapy and regenerative medicine.Molecular therapy. Nucleic acids · 2025Review
- Klotho protein alleviates heart ischemia/reperfusion injury and oxidative stress through regulation of the NOS/MMP pathway.Scientific reports · 2025Article
- Vitamin B12 modulates D-galactose-induced renal dysfunction.The Indian journal of medical research · 2025Article
- Elevated cerebrospinal fluid levels of SERPIN E1 in participants with lewy body diseases.NPJ Parkinson's disease · 2025Article
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Unveiling the Therapeutic Potential of Dulaglutide in Mitigating Tacrolimus-Induced Nephrotoxicity Through Targeting the miR-22/HMGB-1/TLR4/MyD88/NF-κB Trajectory.Archiv der Pharmazie · 2025Article
- Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm.International journal of molecular sciences · 2025Review
- Matrix stiffness in osteoarthritis: from mechanism introduction to biomaterial-based therapies.Frontiers in endocrinology · 2025Review
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- The association of Serum Klotho with the prevalence of cardiovascular disease and prognosis in general population: results from the National Health and Nutrition Examination Survey 2007-2016.Journal of geriatric cardiology : JGC · 2024Article
- Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression.NPJ precision oncology · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements. Klotho inhibited the PI3K/AKT-mediated phosphorylation of FoxO3a and enhanced FoxO3a binding to the MnSOD promoter. Klotho increased MnSOD mRNA and protein expression in mitochondria. In addition, Klotho reduced Tac-induced mitochondrial dysfunction and decreased mitochondrial reactive oxygen species production, and these effects were enhanced by blocking PI3K activity with LY294002. Collectively, our data showed that Klotho protects Tac-induced oxidative stress by negatively regulating the PI3K/AKT pathway and subsequently enhancing FoxO3a-mediated MnSOD expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.