Does the Urothelium of Old Mice Regenerate after Chitosan Injury as Quickly as the Urothelium of Young Mice?

Eva Erzar,Andreja Erman,Katja Lakota,Peter Veranič,Mojca Kerec Kos

doi:10.3390/ijms21103502

Abstract

The aging of organisms leads to a decreased ability of tissue to regenerate after injury. The regeneration of the bladder urothelium after induced desquamation with biopolymer chitosan has been studied in young mice but not in old mice. Chitosan is a suitable inducer of urothelial desquamation because it is known to be non-toxic. We used chitosan for desquamation of urothelial cells in order to compare the dynamics of urothelial regeneration after injury between young and old mice. Our aim was to determine whether the urothelial function and structure of old mice is restored as fast as in young mice, and to evaluate the inflammatory response due to chitosan treatment. We discovered that the urothelial function restored comparably fast in both age groups and that the urothelium of young and old mice recovered within 5 days after injury, although the onset of proliferation and differentiation appeared later in old mice. Acute inflammation markers showed some differences in the inflammatory response in young versus old mice, but in both age groups, chitosan caused short-term acute inflammation. In conclusion, the restoration of urothelial function is not impaired in old mice, but the regeneration of the urothelial structure in old mice slightly lags behind the regeneration in young mice.

Highlights

The urinary bladder epithelium, called urothelium, is one of the most frequent targets of bacterial attacks on human tissues, especially in elderly women [1,2,3]
To evaluate the functional barrier integrity of the urothelium of young and old mice, transepithelial electrical resistance (TEER) measurements were performed in ex vivo conditions (Figure 1)
In the first 30 min of the experiment, the tissue was allowed to recover after the stress induced by the excision of the urinary bladder from the animal, and the TEER value at the end of this period was taken as the baseline value (i.e., 100%) to calculate the relative TEER

Summary

Introduction

The urinary bladder epithelium, called urothelium, is one of the most frequent targets of bacterial attacks on human tissues, especially in elderly women [1,2,3]. The luminal side of the mouse urinary bladder wall is covered by three-layered urothelium. It consists of undifferentiated basal cells at the basal lamina, partly differentiated intermediate cells, and terminally differentiated superficial cells called umbrella cells, which are in contact with the urine in the lumen of the urinary bladder [9]. The blood–urine permeability barrier is maintained by superficial cells, which have a specialized apical plasma membrane with specific transmembrane proteins called uroplakins. In the subapical region of the cytoplasm of umbrella cells, specific plaque-bearing vesicles called fusiform vesicles are concentrated, delivering uroplakins to the apical membrane, and a cytokeratin 20-network, which replaces actin filaments that disappear during urothelial cell differentiation [9,12,13,14]. An impermeable apical plasma membrane of umbrella cells together with well-developed tight junctions between them prevents the transcellular and paracellular passage of molecules through the urothelium [15,16]

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