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Nuclear p120 catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junctions
Ying-Ting Zhu, Hung-Chi Chen, Szu-Yu Chen, Scheffer C. G. Tseng


Contact inhibition ubiquitously exists in non-transformed cells that are in contact with neighboring cells. This phenomenon explains the poor regenerative capacity of in vivo human corneal endothelial cells during aging, injury and surgery. This study demonstrated that the conventional approach of expanding human corneal endothelial cells by disrupting contact inhibition with EDTA followed by bFGF activated canonical Wnt signaling and lost the normal phenotype to endothelial–mesenchymal transition, especially if TGFβ1 was added. By contrast, siRNA against p120 catenin (CTNND1) also uniquely promoted proliferation of the endothelial cells by activating trafficking of p120 catenin to the nucleus, thus relieving repression by nuclear Kaiso. This nuclear p120-catenin–Kaiso signaling is associated with activation of RhoA–ROCK signaling, destabilization of microtubules and inhibition of Hippo signaling, but not with activation of Wnt–β-catenin signaling. Consequently, proliferating human corneal endothelial cells maintained a hexagonal shape, with junctional expression of N-cadherin, ZO-1 and Na+/K+-ATPase. Further expansion of human corneal endothelial monolayers with a normal phenotype and a higher density was possible by prolonging treatment with p120 catenin siRNA followed by its withdrawal. This new strategy of perturbing contact inhibition by selective activation of p120-catenin–Kaiso signaling without disrupting adherent junction could be used to engineer surgical grafts containing normal human corneal endothelial cells to meet a global corneal shortage and for endothelial keratoplasties.


  • Funding

    This study has been supported by the National Eye Institute, National Institutes of Health [grant number R43 EY 022502 to Y.-T.Z. and S.C.G.T.]; and in part by TissueTech, Miami, FL. Deposited in PMC for release after 12 months.

  • Supplementary material available online at

  • Accepted March 22, 2012.
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