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Fast calcium wave inhibits excessive apoptosis during epithelial wound healing

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Abstract

Successful wound closure is mainly the result of two cellular processes: migration and proliferation. Apoptosis has also been suggested to play a role in the mechanisms of wound healing. The fast calcium wave (FCW), triggered immediately after a wound is produced, has been proposed to be involved in determining healing responses in epithelia. We have explored the effects of the reversible inhibition of FCW on the apoptotic and proliferative responses of healing bovine corneal endothelial (BCE) cells in culture. The most important findings of this study are that caspase-dependent apoptosis occurs during the healing process, that the amount of apoptosis has a linear dependence on the migrated distance, and that FCW inhibition greatly increases the apoptotic index. We have further been able to establish that FCW plays a role in the control of cell proliferation during BCE wound healing. These results indicate that one of the main roles of the wave is to inhibit an excessive apoptotic response of the healing migrating cells. This property might represent a basic mechanism to allow sufficient migration and proliferation of the healing cells to assure proper restitution of the injured tissue.

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Acknowledgments

We thank Frigorífico Las Piedras, Frigorífico Lorsinal S.A., and the Ecole Nationale Vétérinaire d’Alfort for supplying us with fresh bovine eyes. We are also grateful to the anonymous reviewers for their useful criticisms and suggestions.

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Correspondence to Silvia Chifflet.

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No conflicts of interest, financial or otherwise, are declared by the authors.

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This study was supported by Cooperation Program ECOS Sud France-Uruguay Grant U08H01 (to A. Torriglia and S. Chifflet); Comisión Sectorial de Investigación Científica (CSIC), Universidad de la República, Uruguay (Proyecto Grupos I+D 2014 to S. Chifflet and Magister and Doctoral Fellowships to C. Justet); and Programa de Desarrollo de las Ciencias Básicas (PEDECIBA), Uruguay (to S. Chifflet and J. A. Hernandez).

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Justet, C., Hernández, J.A., Torriglia, A. et al. Fast calcium wave inhibits excessive apoptosis during epithelial wound healing. Cell Tissue Res 365, 343–356 (2016). https://doi.org/10.1007/s00441-016-2388-8

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