Evidence map›Paper›PMID 25751064›Full record

ArticleThe Journal of clinical investigation2015

KIM-1-mediated phagocytosis reduces acute injury to the kidney.

Li Yang, Craig R Brooks, Sheng Xiao, Venkata Sabbisetti, Melissa Y Yeung, Li-Li Hsiao, Takaharu Ichimura, Vijay Kuchroo, Joseph V Bonventre

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
223citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

223 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Apoptotic Bodies in Kidney Disease: Orchestrators of Inflammation, Fibrosis, and Repair.Journal of the American Society of Nephrology : JASN · 2026
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

163 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Li Yang
Craig R Brooks
Sheng Xiao
Venkata Sabbisetti
Melissa Y Yeung
Li-Li Hsiao
Takaharu Ichimura
Vijay Kuchroo
Joseph V Bonventre

Funding

KIDNEY INJURY MOLECULE-1 IN EPITHELIAL REPAIRR01DK072381 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2005 to 2025
$8.6M
Mechanisms of Ischemic Kidney Injury and RepairR01DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JOSEPH VINCENT BONVENTRE · 1987 to 2026
$6.2M
Mechanisms of Ischemic Kidney Injury and RepairR37DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 1993 to 2021
$5.2M
The role of Tim-1 in immune regulation and autoimmunityK01DK090105 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI XIAO, SHENG · 2011 to 2015
$796k
Proximal tubule Kim-1 expression modulates acute and chronic kidney injuryK01DK099473 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROOKS, CRAIG ROBERT · 2013 to 2017
$787k
Kim-1 regulation of autophagy and MHC presentation in kidney injuryF32DK088418 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BROOKS, CRAIG ROBERT · 2010 to 2012
$153k
NIDDK NIH HHS DK088418NIDDK NIH HHS DK39773NIDDK NIH HHS DK72381NIDDK NIH HHS F32 DK088418NIDDK NIH HHS K01 DK090105NIDDK NIH HHS K01 DK099473NIDDK NIH HHS R01 DK039773NIDDK NIH HHS R01 DK072381NIDDK NIH HHS R37 DK039773
6 · The paper itself

Abstract

Kidney injury molecule 1 (KIM-1, also known as TIM-1) is markedly upregulated in the proximal tubule after injury and is maladaptive when chronically expressed. Here, we determined that early in the injury process, however, KIM-1 expression is antiinflammatory due to its mediation of phagocytic processes in tubule cells. Using various models of acute kidney injury (AKI) and mice expressing mutant forms of KIM-1, we demonstrated a mucin domain-dependent protective effect of epithelial KIM-1 expression that involves downregulation of innate immunity. Deletion of the mucin domain markedly impaired KIM-1-mediated phagocytic function, resulting in increased proinflammatory cytokine production, decreased antiinflammatory growth factor secretion by proximal epithelial cells, and a subsequent increase in tissue macrophages. Mice expressing KIM-1Δmucin had greater functional impairment, inflammatory responses, and mortality in response to ischemia- and cisplatin-induced AKI. Compared with primary renal proximal tubule cells isolated from KIM-1Δmucin mice, those from WT mice had reduced proinflammatory cytokine secretion and impaired macrophage activation. The antiinflammatory effect of KIM-1 expression was due to the interaction of KIM-1 with p85 and subsequent PI3K-dependent downmodulation of NF-κB. Hence, KIM-1-mediated epithelial cell phagocytosis of apoptotic cells protects the kidney after acute injury by downregulating innate immunity and inflammation.

Indexed as

Acute Kidney InjuryAnimalsApoptosisCisplatinCytokinesEpithelial CellsExtracellular Matrix ProteinsGene Expression RegulationHepatitis A Virus Cellular Receptor 1Homeodomain ProteinsImmunity, InnateInflammationIntercellular Signaling Peptides and ProteinsKidneyKidney Tubules, ProximalLLC-PK1 CellsCisplatinCytokinesEcm1 protein, mouseExtracellular Matrix ProteinsHavcr1 protein, mouseHepatitis A Virus Cellular Receptor 1Homeodomain ProteinsIntercellular Signaling Peptides and ProteinsMembrane ProteinsNF-kappa BPhosphatidylinositol 3-KinasesRAG-1 protein

Identifiers

PMID25751064
PMCPMC4396492

What OpenQuestion holds

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Registered trials

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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.