Journal
FASEB JOURNAL
Volume 35, Issue 1, Pages -Publisher
WILEY
DOI: 10.1096/fj.201903105R
Keywords
Akt; Alx; angiogenesis; endothelial cell; vitreous
Categories
Funding
- Department of central laboratory (Xiangya hospital)
- Schepens eye research institute (Massachusetts Eye and Ear Infirmary)
- Science and Technology Plan Project of Hunan Province [2019RS2011]
- National Natural Science Foundation of China [8197413, 81900893]
- NIH [R01EY01250]
- Natural Science Foundation of Hunan [33030135080]
- Laboratory of Medical Genetics (Central South University)
- Department Research to Prevent Blindness
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The research found that vitreous promotes angiogenesis in vitro and revealed that Axl is one of the important receptor tyrosine kinases involved in this process.
Vitreous has been reported to prevent tumor angiogenesis, but our previous findings indicate that vitreous activate the signaling pathway of phosphoinositide 3-kinase (PI3K)/Akt, which plays a critical role in angiogenesis. The goal of this research is to determine which role of vitreous plays in angiogenesis-related cellular responses in vitro. We found that in human retinal microvascular endothelial cells (HRECs) vitreous activates a number of receptor tyrosine kinases including Anexelekto (Axl), which plays an important role in angiogenesis. Subsequently, we discovered that depletion of Axl using CRISPR/Cas9 and an Axl-specific inhibitor R428 suppress vitreous-induced Akt activation and cell proliferation, migration, and tuber formation of HRECs. Therefore, this line of research not only demonstrate that vitreous promotes angiogenesis in vitro, but also reveal that Axl is one of receptor tyrosine kinases to mediate vitreous-induced angiogenesis in vitro, thereby providing a molecular basis for removal of vitreous as cleanly as possible when vitrectomy is performed in treating patients with proliferative diabetic retinopathy.
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