Evidence map›Paper›PMID 39016438›Full record

ArticleAging cell2024

Macrophage iron dyshomeostasis promotes aging-related renal fibrosis.

Lingzhi Wu, Hongchun Lin, Shaomin Li, Yuebo Huang, Yuxiang Sun, Shuangshuang Shu, Ting Luo, Tiantian Liang, Weiyan Lai, Jialing Rao and 2 more

Abstract read
In one paragraph

Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

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

37 citing papers in PubMed.

  1. Review
  2. Article
  3. Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026
    Review
  4. Article
  5. KMT5a-Mediated IRF3 Stabilization Enhances Macrophage Chemotaxis and Renal Fibrosis Progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Engineering Immune Cell to Counteract Aging and Aging-Associated Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  14. Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article
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

12 authors.

Lingzhi WuNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.ORCID 0000-0002-0219-2056
Hongchun LinNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Shaomin LiNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Yuebo HuangNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Yuxiang SunNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Shuangshuang ShuNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Ting LuoNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Tiantian LiangNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Weiyan LaiNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Jialing RaoNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Zhaoyong HuNephrology Division, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Hui PengNephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.ORCID 0000-0002-0220-3616

Funding

China Chronic Kidney Disease Management Innovation Program 202206080010Fundamental Research Funds of Sun Yat-sen University 82000-18843406National Natural Science Foundation of China 81873613National Natural Science Foundation of China 82170762National Natural Science Foundation of China 82370746Natural Science Foundation of Guangdong Province 2022A1515012637Science and Technology Foundation of Guangdong Province of China 2021B1515230005
6 · The paper itself

Abstract

Renal aging, marked by the accumulation of senescent cells and chronic low-grade inflammation, leads to renal interstitial fibrosis and impaired function. In this study, we investigate the role of macrophages, a key regulator of inflammation, in renal aging by analyzing kidney single-cell RNA sequencing data of C57BL/6J mice from 8 weeks to 24 months. Our findings elucidate the dynamic changes in the proportion of kidney cell types during renal aging and reveal that increased macrophage infiltration contributes to chronic low-grade inflammation, with these macrophages exhibiting senescence and activation of ferroptosis signaling. CellChat analysis indicates enhanced communications between macrophages and tubular cells during aging. Suppressing ferroptosis alleviates macrophage-mediated tubular partial epithelial-mesenchymal transition in vitro, thereby mitigating the expression of fibrosis-related genes. Using SCENIC analysis, we infer Stat1 as a key age-related transcription factor promoting iron dyshomeostasis and ferroptosis in macrophages by regulating the expression of Pcbp1, an iron chaperone protein that inhibits ferroptosis. Furthermore, through virtual screening and molecular docking from a library of anti-aging compounds, we construct a docking model targeting Pcbp1, which indicates that the natural small molecule compound Rutin can suppress macrophage senescence and ferroptosis by preserving Pcbp1. In summary, our study underscores the crucial role of macrophage iron dyshomeostasis and ferroptosis in renal aging. Our results also suggest Pcbp1 as an intervention target in aging-related renal fibrosis and highlight Rutin as a potential therapeutic agent in mitigating age-related renal chronic low-grade inflammation and fibrosis.

Indexed as

AgingFibrosisIronMacrophagesMice, Inbred C57BLAnimalsCellular SenescenceFerroptosisHomeostasisHumansKidneyKidney DiseasesMaleMiceIronaging‐related renal fibrosisferroptosisiron dyshomeostasismacrophagepcbp1rutinsingle‐cell RNA sequencing datastat1

Identifiers

PMID39016438
PMCPMC11561705

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.