Angiogenesis, the outgrowth of new blood vessels from existing vasculature, is critical during development, tissue formation, and wound healing. In response to vascular endothelial growth factors (VEGFs), endothelial cells are activated to proliferate and move towards the signal, extending the vessel. These events are directed by VEGF-VEGF receptor (Vegfr2) signal transduction, which in turn is modulated by heparan sulfate proteoglycans (HSPGs). HSPGs are glycoproteins covalently attached to HS glycosaminoglycan chains. Transmembrane protein 184a (Tmem184a) has been recently identified as a heparin receptor, which is believed to bind heparan sulfate chains . Therefore, Tmem184a has the potential to fine-tune interactions between VEGF and HS, modulating Vegfr2-dependent angiogenesis. The function of Tmem184a has been investigated in the regenerating zebrafish caudal fin, but its role has yet to be evaluated during developmental angiogenesis. Here we provide insights into how Tmem184a contributes to the proper formation of the vasculature in zebrafish embryos. First, we find that knockdown of Tmem184a causes a reduction in the number of intact intersegmental vessels (ISVs) in the zebrafish embryo. This phenotype mimics that of knockout mutants, which have previously been shown to exhibit severe defects in ISV development. We then test the importance of HS interactions by removing the binding domain within the Tmem184a protein, which has a negative effect on angiogenesis. Tmem184a is found to act synergistically with Vegfr2b, indicating that the two gene products function in a common pathway to modulate angiogenesis. Moreover, we find that knockdown of Tmem184a leads to an increase in endothelial cell proliferation but a decrease in the amount of VE-cadherin present. Together, these findings suggest that Tmem184a is necessary for ISVs to organize into mature, complete vessels.
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http://dx.doi.org/10.3389/fphys.2022.845407 | DOI Listing |
Transl Lung Cancer Res
January 2024
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Background: Immunotherapy has opened up a new era of individualized treatment for non-small cell lung cancer (NSCLC) with negative driver gene mutations. Anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies have been the main options for immunotherapy over the past decade. Screening for predictive markers of anti-PD-1/PD-L1-responsive patients remains a focus in the field of immunotherapy, especially on the protein level in which relevant proteomic biomarkers are still lacking.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
April 2023
Department of Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Environ Epidemiol
October 2022
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Unlabelled: Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM affects physiology could be through altering DNA methylation (DNAm).
View Article and Find Full Text PDFFront Physiol
September 2022
Department of Biological Sciences, Lehigh University, Bethlehem, PA, United States.
Ann Transl Med
April 2022
Department of Emergency Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Background: Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. This study aimed to identify several mutations associated with vascular intestinal obstruction.
Methods: Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction.
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