ArticleJournal of applied physiology (Bethesda, Md. : 1985)2016
αKlotho deficiency in acute kidney injury contributes to lung damage.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Liuweidihuang Pill Attenuates Early Bleomycin-Induced Pulmonary Fibrosis in Mice and Is Associated with Gut Microbiome.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Decoding lung-kidney interactions in sepsis: an integrated view of molecular mechanisms, pathophysiology, and therapeutic interventions.Frontiers in immunology · 2026Review
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Traffic jam in lung capillaries: inter-organ communication impedes gas exchange after acute kidney injury.The Journal of clinical investigation · 2025Article
- Interorgan communication networks in the kidney-lung axis.Nature reviews. Nephrology · 2024Review
- U-shaped association between serum Klotho and all-cause mortality in US cardiovascular patients: a prospective cohort study.Frontiers in endocrinology · 2024Article
- Exogenous Klotho Extends Survival in COVID-19 Model Mice.Pathogens (Basel, Switzerland) · 2023Article
- Organ Crosstalk in Acute Kidney Injury: Evidence and Mechanisms.Journal of clinical medicine · 2022Review
- Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway.Bioengineered · 2022Article
- Physiologic Regulation of Systemic Klotho Levels by Renal CaSR Signaling in Response to CaSR Ligands and pH o.Journal of the American Society of Nephrology : JASN · 2021Article
- Constitutive transgenic α-Klotho overexpression enhances resilience to and recovery from murine acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Upregulation of antioxidant nuclear factor erythroid 2-related factor 2 and its dependent genes associated with enhancing renal ischemic preconditioning renoprotection using levosimendan and cilostazol in an ischemia/reperfusion rat model.Archives of medical science : AMS · 2021Article
- Klotho: a link between cardiovascular and non-cardiovascular mortality.Clinical kidney journal · 2020Article
- Inhalational delivery of induced pluripotent stem cell secretome improves postpneumonectomy lung structure and function.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Identification of MicroRNA-92a-3p as an Essential Regulator of Tubular Epithelial Cell Pyroptosis by Targeting Nrf1 via HO-1.Frontiers in genetics · 2020Article
- Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung.FASEB bioAdvances · 2019Article
- Renal Klotho is Reduced in Septic Patients and Pretreatment With Recombinant Klotho Attenuates Organ Injury in Lipopolysaccharide-Challenged Mice.Critical care medicine · 2018Article
- Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men.European journal of epidemiology · 2018Article
- Alpha-Klotho Enrichment in Induced Pluripotent Stem Cell Secretome Contributes to Antioxidative Protection in Acute Lung Injury.Stem cells (Dayton, Ohio) · 2018Article
- Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target inefficiently spliced in renal disease.JCI insight · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI.
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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.