Evidence map›Paper›PMID 40760447›Full record

ArticleInflammation and regeneration2025

APJ regulates the balance between self-renewal and differentiation of vascular endothelial stem cells.

Man Wang, Fitriana Nur Rahmawati, Wenting Li, Zeynep Bal, Faya Nuralda Sitompul, Fumitaka Muramatsu, Weizhen Jia, Nobuyuki Takakura

Abstract read
In one paragraph

Article in Inflammation and regeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Man WangDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Fitriana Nur RahmawatiDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Wenting LiDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Zeynep BalDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Faya Nuralda SitompulDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Fumitaka MuramatsuDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Weizhen JiaDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Nobuyuki TakakuraDepartment of Signal Transduction, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan. ntakaku@biken.osaka-u.ac.jp.

Funding

Japan Agency for Medical Research and Development 24ama221533h0001Japan Agency for Medical Research and Development 24ck0106727h0003Japan Agency for Medical Research and Development 25ama221533h0002Japan Society for the Promotion of Science 20H05698Japan Society for the Promotion of Science 25H00444MEXT JPMXP1323015484
6 · The paper itself

Abstract

backgroundCD157 marks a population of tissue-resident vascular endothelial stem cells (VESCs) in mice known for their critical role in homeostatic endothelial cell (EC) turnover and the rapid response to vascular damage in the liver by regeneration. Nevertheless, the mechanism underlying the maintenance and differentiation of postnatal VESCs under both physiological and pathological conditions remains unclear.

methodsAPJ knockout (KO) mice were utilized to explore the role of apelin/APJ signaling in VESC functionality. Flow cytometry, colony-forming unit assays, and in vitro differentiation experiments were conducted to characterize VESC populations. Partial hepatectomy (PHx) was performed to assess vascular regeneration.

resultsAPJ deficiency led to an accumulation of VESCs in the liver of adult mice, which displayed enhanced colony-forming capacity but delayed differentiation into mature ECs. APJ KO mice exhibited impaired vascular regeneration following PHx, linked to compromised VESC differentiation. Transcriptomic analysis revealed upregulation of transcription factors EGR1 and EGR2 and downregulation of Ccnd1 in APJ KO VESCs, implicating disrupted cell cycle regulation. Additionally, APJ deletion reduced collagen IV levels, weakening the basement membrane and contributing to the maintenance of VESCs in an undifferentiated state.

conclusionAPJ signaling is critical for balancing VESC self-renewal and differentiation. APJ deficiency disrupts this balance, leading to impaired vascular regeneration in the liver due to delayed VESC differentiation. This defect is associated with altered transcriptional regulation, favoring a proliferative, undifferentiated state and extracellular matrix changes that weaken structural integrity. These findings highlight the apelin/APJ pathway as a potential therapeutic target to enhance vascular regeneration in regenerative medicine.

Indexed as

Endothelial cell differentiationEndothelial cellsEndothelial stem cellsVascular repair

Identifiers

PMID40760447
PMCPMC12323185

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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.