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      Interleukin-1β-induced Wnt5a enhances human corneal endothelial cell migration through regulation of Cdc42 and RhoA.

      1 , 2
      Molecular and cellular biology

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          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.

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          Author and article information

          Journal
          Mol. Cell. Biol.
          Molecular and cellular biology
          1098-5549
          0270-7306
          Sep 15 2014
          : 34
          : 18
          Affiliations
          [1 ] USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
          [2 ] USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA heur@med.usc.edu.
          Article
          MCB.01572-13
          10.1128/MCB.01572-13
          4135619
          25022753
          52df4c30-842f-4f86-9e27-ec486e8534e2
          Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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