ArticleJournal of the American Society of Nephrology : JASN2015
The macrophage mediates the renoprotective effects of endotoxin preconditioning.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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
38 citing papers in PubMed, 55 citations in OpenAlex.
- Spatiotemporal Control of Intercellular Crosstalk: A New Therapeutic Paradigm for Halting Acute Kidney Injury to Chronic Kidney Disease Transition.Biomolecules · 2026Review
- CX3CL1 deficiency ameliorates acute kidney injury by inhibiting macrophage mitochondrial dysfunction and mtDNA-cGAS-STING signaling.Cell death discovery · 2025Article
- Molecular Mechanisms of Sepsis-Associated Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Review
- Progression of Kidney Fibrosis after Sepsis: Underestimated Role of Resident Macrophages and Recruited Monocytes.Journal of the American Society of Nephrology : JASN · 2025Review
- The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule.The American journal of pathology · 2025Review
- Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.The Journal of clinical investigation · 2024Article
- Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing.bioRxiv : the preprint server for biology · 2023Article
- Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.Nature reviews. Nephrology · 2023Review
- A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.Kidney international · 2023Article
- Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition.Frontiers in molecular biosciences · 2022Review
- Lipopolysaccharide Preconditioning Augments Phagocytosis of Malaria-Parasitized Red Blood Cells by Bone Marrow-Derived Macrophages in the Liver, Thereby Increasing the Murine Survival after Plasmodium yoelii Infection.Infection and immunity · 2021Article
- Integration of spatial and single-cell transcriptomics localizes epithelial cell-immune cross-talk in kidney injury.JCI insight · 2021Article
- The Indiana O'Brien Center for Advanced Renal Microscopic Analysis.American journal of physiology. Renal physiology · 2021Review
- Article
- Toll-Like Receptors in Acute Kidney Injury.International journal of molecular sciences · 2021Review
- Septic acute kidney injury: a review of basic research.Clinical and experimental nephrology · 2020Review
- The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury.Journal of the American Society of Nephrology : JASN · 2020Article
- Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel.Science translational medicine · 2019Article
- The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration.The Journal of clinical investigation · 2019Article
- Flagellin attenuates experimental sepsis in a macrophage-dependent manner.Critical care (London, England) · 2019Article
Corrections and comments
- Commented on by
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Preconditioning is a preventative approach, whereby minimized insults generate protection against subsequent larger exposures to the same or even different insults. In immune cells, endotoxin preconditioning downregulates the inflammatory response and yet, preserves the ability to contain infections. However, the protective mechanisms of preconditioning at the tissue level in organs such as the kidney remain poorly understood. Here, we show that endotoxin preconditioning confers renal epithelial protection in various models of sepsis in vivo. We also tested the hypothesis that this protection results from direct interactions between the preconditioning dose of endotoxin and the renal tubules. This hypothesis is on the basis of our previous findings that endotoxin toxicity to nonpreconditioned renal tubules was direct and independent of immune cells. Notably, we found that tubular protection after preconditioning has an absolute requirement for CD14-expressing myeloid cells and particularly, macrophages. Additionally, an intact macrophage CD14-TRIF signaling pathway was essential for tubular protection. The preconditioned state was characterized by increased macrophage number and trafficking within the kidney as well as clustering of macrophages around S1 proximal tubules. These macrophages exhibited increased M2 polarization and upregulation of redox and iron-handling molecules. In renal tubules, preconditioning prevented peroxisomal damage and abolished oxidative stress and injury to S2 and S3 tubules. In summary, these data suggest that macrophages are essential mediators of endotoxin preconditioning and required for renal tissue protection. Preconditioning is, therefore, an attractive model to investigate novel protective pathways for the prevention and treatment of sepsis.
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.