Background: In sprouting angiogenesis, VEGFR2 level is regulated via a fine-tuned process involving various signaling pathways. Other than VEGF/VEGFR2 signaling pathway, Wnt/ β-catenin signaling is also important in vascular development. However, the crosstalk between these two signaling pathways is still unknown to date. In this study, we aimed to investigate the role of DIX domain containing 1 (DIXDC1) in vasculature, facilitating the crosstalk between VEGF/VEGFR2 and Wnt/ β-catenin signaling pathways.
Results: In mice, DIXDC1 deficiency delayed angiogenesis at the embryonic stage and suppressed neovascularization at the neonatal stage. DIXDC1 knockdown inhibited VEGF-induced angiogenesis in endothelial cells in vitro by downregulating VEGFR2 expression. DIXDC1 bound Dishevelled Segment Polarity Protein 2 (Dvl2) and polymerized Dvl2 stabilizing VEGFR2 protein via its direct interaction. The complex formation and stability of VEGFR2 was potentiated by Wnt signaling. Moreover, hypoxia elevated DIXDC1 expression and likely modulated both canonical Wnt/β-catenin signaling and VEGFR2 stability in vasculatures. Pathological angiogenesis in DIXDC1 knockout mice was decreased significantly in oxygen-induced retinopathy (OIR) and in wound healing models. These results suggest that DIXDC1 is an important factor in developmental and pathological angiogenesis.
Conclusion: We have identified DIXDC1 as an important factor in early vascular development. These results suggest that DIXDC1 represents a novel regulator of sprouting angiogenesis that links Wnt signaling and VEGFR2 stability and may have a potential role in pathological neovascularization.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830128 | PMC |
| http://dx.doi.org/10.1186/s12915-022-01240-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.
Mol Carcinog
July 2024
School of Basic Medicine, Hubei University of Medicine, Shiyan, China.
Article Synopsis
- ACAA2 is an important enzyme in fatty acid metabolism and is linked to tumor development and progression, especially in ovarian cancer, though its exact role was previously unclear.
- Research analyzed ACAA2's expression, conducted functional experiments, and utilized RNA-seq to uncover its regulatory mechanisms in ovarian cancer.
- Findings suggest that ACAA2 promotes cancer cell growth and spread, possibly through the WNT/β-Catenin pathway, indicating it may serve as an oncogene and a potential therapeutic target in ovarian cancer treatment.
Screening of novel biomarkers for breast cancer based on WGCNA and multiple machine learning algorithms.
Transl Cancer Res
June 2023
Department of Thyroid and Breast Surgery, Nantong City No. 1 People's Hospital and Second Affiliated Hospital of Nantong University, Nantong, China.
Background: Breast cancer (BC) ranks first in incidence among women, with approximately 2 million new cases per year. Therefore, it is essential to investigate emerging targets for BC patients' diagnosis and prognosis.
Methods: We analyzed gene expression data from 99 normal and 1,081 BC tissues in The Cancer Genome Atlas (TCGA) database.
Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m modification.
Mol Ther
August 2023
Spine Labs, St. George & Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Spine Service, Department of Orthopedic Surgery, St. George Hospital, Kogarah, NSW, Australia. Electronic address:
Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease.
View Article and Find Full Text PDFQuantitative trait loci on chromosomes 9 and 19 modulate AII amacrine cell number in the mouse retina.
Front Neurosci
February 2023
Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, United States.
Sequence variants modulating gene function or expression affect various heritable traits, including the number of neurons within a population. The present study employed a forward-genetic approach to identify candidate causal genes and their sequence variants controlling the number of one type of retinal neuron, the AII amacrine cell. Data from twenty-six recombinant inbred (RI) strains of mice derived from the parental C57BL/6J (B6/J) and A/J laboratory strains were used to identify genomic loci regulating cell number.
View Article and Find Full Text PDFIdentification of candidate genes for nicotine withdrawal in C57BL/6J × DBA/2J recombinant inbred mice.
Genes Brain Behav
April 2023
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Article Synopsis
- * A study involving recombinant inbred mice found significant genetic associations related to somatic withdrawal signs and anxiety-like behaviors, particularly linked to specific genes on chromosomes 14 and 9.
- * The research identified candidate genes (like Rb1 and Galr1) that could be potential targets for future therapies to alleviate nicotine withdrawal symptoms based on genetic and gene expression analysis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!