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2017 ; 312
(4
): F732-F743
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Sleeping beauty: awakening urothelium from its slumber
#MMPMID28122714
Balsara ZR
; Li X
Am J Physiol Renal Physiol
2017[Apr]; 312
(4
): F732-F743
PMID28122714
show ga
The bladder urothelium is essentially quiescent but regenerates readily upon
injury. The process of urothelial regeneration harkens back to the process of
urothelial development whereby urothelial stem/progenitor cells must proliferate
and terminally differentiate to establish all three urothelial layers. How the
urothelium regulates the level of proliferation and the timing of differentiation
to ensure the precise degree of regeneration is of significant interest in the
field. Without a carefully-orchestrated process, urothelial regeneration may be
inadequate, thereby exposing the host to toxins or pathogens. Alternatively,
regeneration may be excessive, thereby setting the stage for tumor development.
This review describes our current understanding of urothelial regeneration. The
current controversies surrounding the identity and location of urothelial
progenitor cells that mediate urothelial regeneration are discussed and evidence
for each model is provided. We emphasize the factors that have been shown to be
crucial for urothelial regeneration, including local growth factors that
stimulate repair, and epithelial-mesenchymal cross talk, which ensures feedback
regulation. Also highlighted is the emerging concept of epigenetic regulation of
urothelial regeneration, which additionally fine tunes the process through
transcriptional regulation of cell cycle genes and growth and differentiation
factors. Finally, we emphasize how several of these pathways and/or programs are
often dysregulated during malignant transformation, further corroborating their
importance in directing normal urothelial regeneration. Together, evidence in the
field suggests that any attempt to exploit regenerative programs for the purposes
of enhanced urothelial repair or replacement must take into account this delicate
balance.
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