Affiliation:
1. USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
Abstract
ABSTRACT
Wnt5a can activate β-catenin-independent pathways for regulation of various cellular functions, such as migration, that play critical roles in wound repair. Investigation of Wnt5a signaling may help identify therapeutic targets for enhancing corneal endothelial wound healing that could provide an alternative to corneal transplantation in patients with blindness from endothelial dysfunction. However, Wnt5a signaling in corneal endothelial cells (CECs) has not been well characterized. In this study, we show transient induction of Wnt5a by interleukin-1β (IL-1β) stimulation proceeds through NF-κB in human CECs. This leads to binding of Fzd5 to Ror2, resulting in activation of disheveled protein (Dvl) and subsequently disheveled-associated activator of morphogenesis 1 (DAAM1). This leads to activation of Cdc42 and subsequent inhibition of RhoA. Inhibition of RhoA leads to parallel dephosphorylation and inactivation of LIM domain kinase 2 along with dephosphorylation and activation of slingshot 1, resulting in dephosphorylation and activation of cofilin and leading to enhanced cell migration. These findings suggest that Wnt5a enhances cell migration through activation of Cdc42 and inactivation of RhoA in human CECs.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference70 articles.
1. Expression of cell cycle-associated proteins in human and rabbit corneal endothelium in situ;Joyce NC;Invest. Ophthalmol. Vis. Sci.,1996
2. Cell cycle kinetics in corneal endothelium from old and young donors;Senoo T;Invest. Ophthalmol. Vis. Sci.,2000
3. Corneal blindness: a global perspective;Whitcher JP;Bull. World Health Organ.,2001
4. Induction of FGF-2 Synthesis by IL-1β in Aqueous Humor through P13-Kinase and p38 in Rabbit Corneal Endothelium
5. Inhibition of Inflammatory Cytokine Production in Human Corneal Cells by Dexamethasone, but Not Cyclosporin
Cited by
41 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献