TY - JOUR
T1 - ANKFY1 is essential for retinal endothelial cell proliferation and migration via VEGFR2/Akt/eNOS pathway
AU - Tanaka, Miruto
AU - Nakamura, Shinsuke
AU - Maekawa, Masashi
AU - Higashiyama, Shigeki
AU - Hara, Hideaki
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Dysregulation of endothelial cell proliferation and migration are hallmarks of angiogenic diseases. Among them, excessive ocular angiogenesis is a major cause of blindness. Vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling plays crucial roles in angiogenesis, endothelial cell proliferation and migration. Here, we showed that ankyrin repeat and FYVE domain containing 1 (ANKFY1), a Rab5-GTP-interacting protein, is required for retinal endothelial cell proliferation and migration. ANKFY1 knockdown significantly suppressed cell growth of human retinal microvascular endothelial cells (HRMECs) in the presence or absence of VEGF. HRMEC migration was also inhibited by depletion of ANKFY1. Western blot analysis showed that ANKFY1 knockdown reduced cell surface VEGFR2 level. In contrast, qRT-PCR analysis indicated that ANKFY1 knockdown had no effect on VEGFR2 mRNA levels. We also found that the attenuation of the protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) pathway in ANKFY1 knockdown HRMECs. In conclusion, our findings revealed novel functions of ANKFY1 in cell growth and migration of retinal endothelial cells.
AB - Dysregulation of endothelial cell proliferation and migration are hallmarks of angiogenic diseases. Among them, excessive ocular angiogenesis is a major cause of blindness. Vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling plays crucial roles in angiogenesis, endothelial cell proliferation and migration. Here, we showed that ankyrin repeat and FYVE domain containing 1 (ANKFY1), a Rab5-GTP-interacting protein, is required for retinal endothelial cell proliferation and migration. ANKFY1 knockdown significantly suppressed cell growth of human retinal microvascular endothelial cells (HRMECs) in the presence or absence of VEGF. HRMEC migration was also inhibited by depletion of ANKFY1. Western blot analysis showed that ANKFY1 knockdown reduced cell surface VEGFR2 level. In contrast, qRT-PCR analysis indicated that ANKFY1 knockdown had no effect on VEGFR2 mRNA levels. We also found that the attenuation of the protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) pathway in ANKFY1 knockdown HRMECs. In conclusion, our findings revealed novel functions of ANKFY1 in cell growth and migration of retinal endothelial cells.
KW - ANKFY1
KW - Akt/eNOS
KW - Endothelial cell proliferation and migration
KW - HRMECs
KW - VEGFR2
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U2 - 10.1016/j.bbrc.2020.10.032
DO - 10.1016/j.bbrc.2020.10.032
M3 - Article
C2 - 33092793
AN - SCOPUS:85092786423
VL - 533
SP - 1406
EP - 1412
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -