Evidence map›Paper›PMID 40764462›Full record

ArticleAngiogenesis2025

UHRF1 in endothelial cells is essential for angiogenesis and associated with the activation of pro-angiogenic signaling pathways and expression of endothelial genes.

Ying Liu, Jiake Mo, Zi Guo, Jiaqi Zhang, Weian Tang, Xubiao Meng, Yufang Luo, Fang Wang, Zhaohui Mo

Abstract read
PubMed Publisher
In one paragraph

Article in Angiogenesis, 2025. 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

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

1 citing paper in PubMed.

  1. 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

9 authors.

Ying Liu *Department of Endocrinology, Department of Endocrinology, The Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, 410013, Hunan Province, China.
Jiake Mo *Department of Endocrinology, Department of Endocrinology, The Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, 410013, Hunan Province, China.
Zi GuoSection of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06510, USA.
Jiaqi ZhangDepartment of Endocrinology, Department of Endocrinology, The Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, 410013, Hunan Province, China.
Weian TangDepartment of Endocrinology, Department of Endocrinology, The Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, 410013, Hunan Province, China.
Xubiao MengDepartment of Endocrinology, Haikou People's Hospital & Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570100, Hainan Province, China.
Yufang LuoClinical Nutrition Department, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan Province, China. lau0325@163.com.
Fang WangDepartment of Endocrinology, Department of Endocrinology, The Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, 410013, Hunan Province, China. wangfang1122@csu.edu.cn.
Zhaohui MoDepartment of Endocrinology, Department of Endocrinology, The Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, 410013, Hunan Province, China. easd04mzh@126.com.

Funding

Hainan Provincial Natural Science Foundation of China 822MS201National Natural Science Foundation of China 81970724Natural Science Foundation of Changsha kq2502210
6 · The paper itself

Abstract

Epigenetics is increasingly recognized as a crucial factor in angiogenesis. Ubiquitin-like with PHD and RING Finger Domains 1 (UHRF1) is an important epigenetic regulatory protein involved in regulating cellular life processes, developing many diseases. However, its potential role in regulating embryonic vascular development and postnatal angiogenesis is unclear. Our study found that endothelial cell-specific UHRF1 knockout mice showed obvious developmental disorders at the embryonic stage (E11.5-15.5), including impaired development of the individual embryo size and organs, sparse vascularity in the yolk sac, or even death. In the lower limb ischemia model, UHRF1 expression in ischemic muscle tissues of mice is proportionate to the regeneration of blood vessels. To confirm the specific inhibition of UHRF1, we transfected an adeno-associated virus serotype 9 which inserted a TIE-2 promoter and mediated the delivery of short hairpin RNA (AAV9-TIE-2-shUHRF1) into mouse vascular endothelial cells to knock down UHRF1 specifically. We observed that the knockdown of UHRF1 in endothelial cells results in poorer lower limb perfusion in mice. Mechanically, UHRF1 knockdown decreased the tube-forming capacity of ECFCs, whereas overexpression of UHRF1 by diabetic ECFCs where UHRF1 expression is typically downregulated significantly increased the tube-forming capacity of the cells. RNAseq and related bioinformatics analyses showed that differentially expressed genes (DEGs) were mainly involved in angiogenesis-related pathways. The results of qPCR and western blot showed that the protein and mRNA levels of angiogenesis-related factors (VEGF, PDGF, and ANGPT1), as well as vascular endothelial surface marker molecules (VEGFR2, CD31, and c-Kit), were down-regulated accordingly. Furthermore, ChIP experiments showed that UHRF1 was able to bind the promoters of VEGFR2 and CD31, affecting the levels of histone-methylated protein (H3K4me3 and H3K27me3) enriched in the promoter region. However, the expression of CD31 and VEGFR2 can be reversed separately after the transformation of different histone-methylated protein levels (H3K4me3 and H3K27me3). Taken together, UHRF1 may regulate angiogenic gene expression and vascular endothelial cell differentiation through epigenetic mechanisms and is essential for angiogenesis.

Indexed as

CCAAT-Enhancer-Binding ProteinsEndothelial CellsNeovascularization, PhysiologicSignal TransductionUbiquitin-Protein LigasesAngiogenesisAnimalsHumansIschemiaMiceMice, KnockoutCCAAT-Enhancer-Binding ProteinsUbiquitin-Protein LigasesUhrf1 protein, mouseAngiogenesisEndothelial differentiationEpigenetic mechanismHistone modificationsUHRF1

Identifiers

PMID40764462

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.