PUBLICATION

HMGA2 contributes to vascular development and sprouting angiogenesis by promoting IGFBP2 production

Authors
Wang, J., Chen, Y., Zeng, Z., Feng, R., Wang, Q., Zhang, Q., Sun, K., Chen, A.F., Lu, Y., Yu, Y.
ID
ZDB-PUB-210922-35
Date
2021
Source
Experimental cell research   408(1): 112831 (Journal)
Registered Authors
Keywords
Angiogenesis. Central arteries defects. HMGA2. IGFBP2. Zebrafish
MeSH Terms
  • Animals
  • Carcinogenesis/metabolism
  • Embryonic Development/physiology
  • HMGA2 Protein/metabolism*
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2/genetics
  • Insulin-Like Growth Factor Binding Protein 2/metabolism*
  • Morphogenesis/physiology*
  • Neoplasms/metabolism
  • Neovascularization, Pathologic/metabolism*
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed
34547256 Full text @ Exp. Cell Res.
Abstract
Angiogenesis is the process by which new blood vessels form from preexisting vessels and regulates the processes of embryonic development, wound healing and tumorigenesis. HMGA2 is involved in the occurrence of several cancers, but its biological role and the exact downstream genes involved in vascular development and sprouting angiogenesis remain largely unknown. Here, we first found that HMGA2 knockdown in zebrafish embryos resulted in defects of central artery formation. RNA sequencing revealed that IGFBP2 was significantly downregulated by interference with HMGA2, and IGFBP2 overexpression reversed the inhibition of brain vascular development caused by HMGA2 deficiency. In vitro, we further found that HMGA2 knockdown blocked the migration, tube formation and branching of HUVECs. Similarly, IGFBP2 protein overexpression attenuated the impairments induced by HMGA2 deficiency. Moreover, the promotion of angiogenesis by HMGA2 overexpression was verified in a Matrigel plug assay. We next found that HMGA2 bound directly to a region in the IGFBP2 promoter and positively regulated IGFBP2 expression. Interestingly, the mRNA expression levels of HMGA2 and IGFBP2 were increased significantly in the peripheral blood of hemangioma patients, indicating that overexpression of HMGA2 and IGFBP2 results in vessel formation, consistent with the results of the in vivo and in vitro experiments. In summary, our findings demonstrate that HMGA2 promotes central artery formation by modulating angiogenesis via IGFBP2 induction.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping