title: Endogenous vascular endothelial growth factor-A (VEGF-A) maintains endothelial cell homeostasis by regulating VEGF receptor-2 transcription.
abstract: Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Guangqi
authors.initials: G
authors.lastname: E
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.forename: Santanu
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Shamit
authors.initials: S
authors.lastname: Dutta
authors.forename: Enfeng
authors.initials: E
authors.lastname: Wang
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D020218:Response Elements / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis* / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C082078:mesenchyme fork head 1 protein; D040301:Vascular Endothelial Growth Factor Receptor-2