Evidence mapPaperPMID 40588562Full record

ArticleEMBO molecular medicine2025

Loss of p300 in proximal tubular cells reduces renal fibrosis and endothelial-mesenchymal transition.

Hyunsik Kim, Soo-Yeon Park, Soo Yeon Lee, Jae-Hwan Kwon, Seunghee Byun, Byounghwi Ko, Jung-Yoon Yoo, Beom Seok Kim, Beom Jin Lim, Ho-Geun Yoon

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

10 authors.

Hyunsik KimDepartment of Biochemistry and Molecular Biology, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.ORCID 0000-0002-9873-9537
Soo-Yeon ParkDepartment of Biochemistry and Molecular Biology, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.ORCID 0000-0003-3743-9554
Soo Yeon LeeDepartment of Biochemistry and Molecular Biology, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.ORCID 0000-0003-2434-7917
Jae-Hwan KwonDepartment of Biochemistry and Molecular Biology, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.
Seunghee ByunDepartment of Biochemistry and Molecular Biology, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.ORCID 0000-0003-1178-7163
Byounghwi KoDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, 03722, Korea.
Jung-Yoon YooDepartment of Biomedical Laboratory Science, Yonsei University MIRAE Campus, Wonju, 26493, Korea.
Beom Seok KimDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, 03722, Korea. docbsk@yuhs.ac.ORCID 0000-0002-5732-2583
Beom Jin LimDepartment of Pathology, Yonsei University College of Medicine, Seoul, 03722, Korea. bjlim@yuhs.ac.ORCID 0000-0003-2856-0133
Ho-Geun YoonDepartment of Biochemistry and Molecular Biology, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea. YHGEUN@yuhs.ac.ORCID 0000-0003-2718-3372

Funding

Korean government (MSIT) No. NRF-2022R1A2C1091055Korean government (MSIT) No. RS-2025-02214844
6 · The paper itself

Abstract

Chronic kidney disease (CKD) has a high prevalence worldwide and is typically accompanied by severe fibrosis. However, the exact pathogenesis of renal fibrosis and effective treatments have yet to be identified. In this study, we found that expression of the histone-acetyltransferase p300 was increased in focal segmental glomerulosclerosis patients and several distinct mouse models of renal fibrosis. Moreover, we showed that the AKT-mediated phosphorylation of Ser-1834 of p300 increased the stability of p300 upon renal fibrosis induction, and conversely, PPM1K specifically dephosphorylated p300 at Ser-1834, resulting in a significant reduction in p300 stability and renal fibrosis. Interestingly, increased p300 in proximal tubular cells (PTCs) promoted renal fibrosis development by mediating the endothelial to mesenchymal transition (EndMT) via upregulation of the mesenchymal-transition-related secreted proteins POSTN, FSTL1, and FSCN1. Both EndMT and renal fibrosis were significantly diminished by either PTC-specific deletion of p300 gene or selective inhibitors of p300. Collectively, our results demonstrate the role of p300 in the development of renal fibrosis, and suggest that p300 is a promising target for treatment of advanced CKD.

Indexed as

E1A-Associated p300 ProteinEpithelial-Mesenchymal TransitionFibrosisKidney Tubules, ProximalAnimalsDisease Models, AnimalEndothelial-Mesenchymal TransitionHumansMaleMiceRenal Insufficiency, ChronicE1A-Associated p300 ProteinEP300 protein, humanChronic Kidney DiseaseEndothelial-mesenchymal Transitionp300Renal Fibrosis, Proximal Tubular Cells

Identifiers

PMID40588562
PMCPMC12254316

What Socratic holds

Textmetadata
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.