Evidence mapPaperPMID 41628890Full record

ArticleKidney3602026

Arginase-1 Expressing Macrophages Interact with Myofibroblasts to Regulate Insulin-Like Growth Factor-1-Dependent Tubule Repair.

Bhavya Bharathan, Bismark O Frimpong, Leyuan Xu, Lloyd G Cantley

Abstract read
In one paragraph

Article in Kidney360, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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

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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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Bhavya BharathanSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Bismark O FrimpongDepartment of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut.ORCID 0000-0002-0689-3968
Leyuan XuSection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.ORCID 0000-0002-3071-9206
Lloyd G CantleySection of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.ORCID 0000-0002-8444-6469

Funding

Macrophage Function in Kidney RepairR01DK093771 · YALE UNIVERSITY · 2025 to 2025
$369k
Targeting immune dysfunction during transition from AKI to CKDR01DK135689 · YALE UNIVERSITY · 2025 to 2025
$369k
NIDDK NIH HHS DK093771NIDDK NIH HHS DK135689NIDDK NIH HHS R01 DK093771NIH HHS R01DK135689
6 · The paper itself

Abstract

key pointsInsulin-like growth factor-1 is upregulated in the injured outer stripe of the kidney only if Arginase-1 (Arg1)-expressing macrophages are present. Arg1-expressing macrophages induce myofibroblasts and endothelial cells of the outer stripe to express insulin-like growth factor-1 rather than making it themselves. Myofibroblast-expressed insulin-like growth factor-1 induces proximal tubule insulin-like growth factor-1 receptor activation and subsequent proliferation.

backgroundFollowing AKI, successful regeneration of tubular epithelium is essential to restore normal kidney function. We have previously reported that arginase-1-expressing macrophages in the outer medulla promote tubular proliferation after ischemic injury; however, the mechanism of this effect remained unidentified.

methodsArginase-1 + macrophage-dependent proliferative signals and their cellular source were determined by cell sorting and single-cell transcriptional profiling at 2 days postinjury in mice subjected to ischemia-reperfusion injury and in vitro using transwell coculture of macrophages and renal cells.

resultsQuantitative PCR analysis of outer medullary RNA on day 2 post-ischemia-reperfusion injury in wild type and macrophage-specific arginase-1 null ( Arg1mko ) mice identified insulin-like growth factor-1 ( Igf1 ) as the epithelial growth factor significantly upregulated in an arginase-1-dependent manner after kidney injury. Single-cell RNA sequencing analysis of mouse kidneys, human kidney biopsies, and sorted outer medullary cells identified myofibroblasts and endothelial cells as potential cellular sources of IGF1. In vitro studies showed that myofibroblast and endothelial cell expression of Igf1 was dependent on macrophage arginase-1 expression and that myofibroblast-secreted IGF1-induced epithelial cell IGF1 receptor activation and proliferation. Consistent with this, in vivo activation of the IGF1 receptor on surviving S3 proximal tubule cells after injury was dependent on macrophage Arg1 expression.

conclusionsOur results demonstrate that alternatively activated macrophages signal cooperatively with myofibroblasts and possibly endothelial cells to coordinate local IGF1 secretion and proliferative tubule repair at sites of epithelial cell loss after kidney injury. These findings support an important role of activated myofibroblasts in effective tubule repair.

Indexed as

Acute Kidney InjuryArginaseInsulin-Like Growth Factor IKidney Tubules, ProximalMacrophagesMyofibroblastsReperfusion InjuryAnimalsCell ProliferationEndothelial CellsHumansMaleMiceMice, Inbred C57BLMice, KnockoutArg1 protein, mouseArginaseInsulin-Like Growth Factor IAKIcell signalingendothelial cellsfibroblastischemia-reperfusionmacrophagesproliferationproximal tubuletubule cells

Identifiers

PMID41628890
PMCPMC13337152

What Socratic 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 Socratic graph.