Gliding Basal Cell Migration of the Urothelium during Wound Healing

Abstract

Collective cell migration during wound healing has been extensively studied in the epidermis. However, it remains unknown whether the urothelium repairs wounds in a manner similar to the epidermis. By in vivo two-photon excitation microscopy of transgenic mice that express fluorescent biosensors, we studied the collective cell migration of the urothelium in comparison with that of the epidermis. In vivo time-lapse imaging revealed that, even in the absence of a wound, urothelial cells continuously moved and sometimes glided as a sheet over the underlying lamina propria. On abrasion of the epithelium, the migration speed of each epidermal cell was inversely correlated with the distance to the wound edge. Repetitive activation waves of extracellular signal-regulated kinase (ERK) were generated at and propagated away from the wound edge. In contrast, urothelial cells glided as a sheet over the lamina propria without any ERK activation waves. Accordingly, the mitogen-activated protein kinase/ERK kinase inhibitor PD0325901 decreased the migration velocity of the epidermis but not the urothelium. Interestingly, the tyrosine kinase inhibitor dasatinib inhibited migration of the urothelium as well as the epidermis, suggesting that the gliding migration of the urothelium is an active, not a passive, migration. In conclusion, the urothelium glides over the lamina propria to fill wounds in an ERK-independent manner, whereas the epidermis crawls to cover wounds in an ERK-dependent manner.