Evidence mapPaperPMID 38615014Full record

ArticleNature communications2024

Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence.

Lingzhi Li, Ting Xiang, Jingjing Guo, Fan Guo, Yiting Wu, Han Feng, Jing Liu, Sibei Tao, Ping Fu, Liang Ma

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
18.0field-weighted citation impact, top 1% of its field
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

71 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

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

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

10 authors at 2 institutions in 2 countries.

Lingzhi Li *Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
Ting Xiang *Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
Jingjing GuoDepartment of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China.
Fan GuoDepartment of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
Yiting WuDepartment of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
Han FengTulane Research and Innovation for Arrhythmia Discoveries-TRIAD Center, Tulane University School of Medicine, New Orleans, LA, USA.
Jing LiuDepartment of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
Sibei TaoDepartment of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China.
Ping FuDepartment of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China. fupinghx@scu.edu.cn.ORCID http://orcid.org/0000-0002-3061-5925
Liang MaDepartment of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, and National Key Laboratory of Kidney Diseases, Chengdu, China. liang_m@scu.edu.cn.ORCID http://orcid.org/0000-0001-8327-7969
Sichuan University · CNTulane University · US

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82100775National Natural Science Foundation of China (National Science Foundation of China) 82370737
6 · The paper itself

Abstract

Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1β, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1β expression, which thereby alleviate IL-1β-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.

Indexed as

HistonesKidney DiseasesAcetate-CoA LigaseCellular SenescenceEpithelial CellsHumansInterleukin-1betaKidneyLysineMacrophage ActivationAcetate-CoA LigaseACSS2 protein, humanHistonesInterleukin-1betaLysine

Identifiers

PMID38615014
PMCPMC11016098
OpenAlexW4394784556

What Socratic holds

Textmetadata
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 Socratic graph.