WNT10B enhances proliferation through ?-catenin and RAC1 GTPase in human corneal endothelial cells.
The cornea is the anterior, transparent tissue of the human eye that serves as its main refractive element. Corneal endothelial cells are arranged as a monolayer on the posterior surface of the cornea and function as a pump to counteract the leakiness of its basement membrane. Maintaining the cornea in ... a slightly dehydrated state is critical for the maintenance of corneal transparency. Adult human corneal endothelial cells are G1-arrested, even in response to injury, leading to an age-dependent decline in endothelial cell density. Corneal edema and subsequent vision loss ensues when endothelial cell density decreases below a critical threshold. Vision loss secondary to corneal endothelial dysfunction is a common indication for transplantation in developed nations. An impending increase in demand for and a current global shortage of donor corneas will necessitate the development of treatments for vision loss because of endothelial dysfunction that do not rely on donor corneas. Wnt ligands regulate many critical cellular functions, such as proliferation, making them attractive candidates for modulation in corneal endothelial dysfunction. We show that WNT10B causes nuclear transport and binding of RAC1 and ?-catenin in human corneal endothelial cells, leading to the activation of Cyclin D1 expression and proliferation. Our findings indicate that WNT10B promotes proliferation in human corneal endothelial cells by simultaneously utilizing both ?-catenin-dependent and -independent pathways and suggest that its modulation could be used to treat vision loss secondary to corneal endothelial dysfunction.
Mesh Terms:
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Cell Line, Transformed, Cell Proliferation, Cornea, Cyclin D1, Dishevelled Proteins, Endothelial Cells, G1 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Humans, Interleukin-1beta, Phosphoproteins, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Signal Transduction, Wnt Proteins, beta Catenin, rac1 GTP-Binding Protein
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Cell Line, Transformed, Cell Proliferation, Cornea, Cyclin D1, Dishevelled Proteins, Endothelial Cells, G1 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Humans, Interleukin-1beta, Phosphoproteins, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Signal Transduction, Wnt Proteins, beta Catenin, rac1 GTP-Binding Protein
J Biol Chem
Date: Oct. 30, 2015
PubMed ID: 26370090
View in: Pubmed Google Scholar
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