Abstract
Using primary explant cultures of mouse bladder, the early response of the urothelium after superficial and full-thickness injuries was investigated. In such an in vitro wound healing model, explant surfaces with a mostly desquamated urothelial superficial layer represented superficial wounds, and the exposed lamina propria at the cut edges of the explants represented full-thickness wounds. The urothelial cell ultrastructure, the expression and subcellular distribution of the tight junctional protein occludin, and differentiation-related proteins CK 20, uroplakins, and actin were followed. Since singular terminally differentiated superficial cells remained on the urothelium after superficial injury (i.e., original superficial cells), we sought to determine their role during the urothelial wound-healing process. Ultrastructural and immunocytochemical studies have revealed that restored tight junctions are the earliest cellular event during the urothelial superficial and full-thickness wound-healing process. Occludin-containing tight junctions are developed before the new superficial cells are terminally differentiated. New insights into the urothelium wound-healing process were provided by demonstrating that the original superficial cells contribute to the urothelium wound healing by developing tight junctions with de novo differentiated superficial cells and by stretching, thus providing a large urothelial surface with asymmetric unit membrane plaques.
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Acknowledgements
The authors thank Prof. Tung-Tien Sun (New York University Medical School) for the generous gift of uroplakin antibodies and Dr. Marko Kreft (LN-MCP Medical Faculty, University of Ljubljana) for the work with the confocal microscope. The study was supported by the Slovenian Ministry of Education, Science and Sport (Grant No. Z3-6046-0381-04).
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Kreft, M.E., Sterle, M., Veranič, P. et al. Urothelial injuries and the early wound healing response: tight junctions and urothelial cytodifferentiation. Histochem Cell Biol 123, 529–539 (2005). https://doi.org/10.1007/s00418-005-0770-9
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DOI: https://doi.org/10.1007/s00418-005-0770-9