PUBLICATION
TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit
- Authors
- Yang, Yinfang, Singh, Angom Ramcharan, Zhao, Yuanyuan, Du, Tao, Huang, Yitong, Wan, Xiaohong, Mukhopadhyay, Debabrata, Wang, Ying, Wang, Nanping, Zhang, Peng
- ID
- ZDB-PUB-200930-1
- Date
- 2020
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34(11): 14710-14724 (Journal)
- Registered Authors
- Mukhopadhyay, Debabrata
- Keywords
- none
- MeSH Terms
-
- Animals
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Hypoxia-Inducible Factor 1/metabolism
- Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Male
- Neovascularization, Physiologic*
- Rats
- Rats, Sprague-Dawley
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Receptors, Vascular Endothelial Growth Factor/genetics
- Receptors, Vascular Endothelial Growth Factor/metabolism
- Signal Transduction*
- Tripartite Motif-Containing Protein 28/genetics
- Tripartite Motif-Containing Protein 28/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- p38 Mitogen-Activated Protein Kinases/metabolism
- PubMed
- 32918765 Full text @ FASEB J.
Citation
Yang, Yinfang, Singh, Angom Ramcharan, Zhao, Yuanyuan, Du, Tao, Huang, Yitong, Wan, Xiaohong, Mukhopadhyay, Debabrata, Wang, Ying, Wang, Nanping, Zhang, Peng (2020) TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 34(11):14710-14724.
Abstract
Sprouting angiogenesis is a highly coordinately process controlled by vascular endothelial growth factor receptor (VEGFR)‐Notch signaling. Here we investigated whether Tripartite motif‐containing 28 (TRIM28), which is an epigenetic modifier implicated in gene transcription and cell differentiation, is essential to mediate sprouting angiogenesis. We observed that knockdown of TRIM28 ortholog in zebrafish resulted in developmental vascular defect with disorganized and reduced vasculatures. Consistently, TRIM28 knockdown inhibited angiogenic sprouting of cultured endothelial cells (ECs), which exhibited increased mRNA levels of VEGFR1, Delta‐like (DLL) 3, and Notch2 but reduced levels of VEGFR2, DLL1, DLL4, Notch1, Notch3, and Notch4.The regulative effects of TRIM28 on these angiogenic factors were partially mediated by hypoxia‐inducible factor 1 α (HIF‐1α) and recombination signal‐binding protein for immunoglobulin kappa J region (RBPJκ). In vitro DNA‐binding assay showed that TRIM28 knockdown increased the association of RBPJκ with DNA sequences containing HIF‐1α‐binding sites. Moreover, the phosphorylation of TRIM28 was controlled by VEGF and Notch1 through a mechanism involving RBPJκ‐dual‐specificity phosphatase (DUSP)‐p38 MAPK, indicating a negative feedback mechanism. These findings established TRIM28 as a crucial regulator of VEGFR‐Notch signaling circuit through HIF‐1α and RBPJκ in EC sprouting angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping