# Retinoic acid signaling controls urothelial development and regeneration.

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $506,061

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Mendelsohn, Cathy Lee
Project Summary
The urothelium is an epithelial barrier that prevents exchange of water and toxic
substances between the blood and urinary tract. It is composed of basal cells,
Intermediate cells and a luminal layer of superficial cells. Superficial cells are
specialized for synthesis and transport of uroplakins, a family of proteins that assemble
into the crystalline apical plaque that is the functional urothelial barrier. Superficial cells
have a number of interesting features; they are enormous, generally binucleated and
are polyploid. The urothelium is one of the most quiescent epithelia in the body, but
quickly regenerates in response to acute damage, for example from urinary tract
infection. Chronic injury however, from repeated exposure to toxins such as
cyclophosphamide, can lead to barrier compromise, inflammation and disease such as
bladder pain syndrome, a life altering condition for which there is no cure at present.
These proposed studies build on previous findings from our lab that identify novel
urothelial progenitors that are important for development and regeneration. In the
present application, we will use lineage analysis and an organ culture together with live
imaging to visualize the behavior of adult wild type and mutant urothelial progenitors.
We will pursue preliminary studies suggesting that Basal cells, which are unipotent
during acute injury, acquire the potential to produce Intermediate and Superficial cell
daughters after chronic injury. We identify Pparg, a nuclear receptor best known for its
role in adipogenesis, as a potential target of Retinoids, and we show that Pparg is
critical for formation and regeneration of Superficial cells, and also regulates basal cell
homeostasis, preventing squamous differentiation. Besides its critical role in human
health, the urothelium is a also source of cells that give rise to different types of bladder
cancers. Identification of urothelial progenitors and the signaling pathways that control
them will be important for developing therapeutic strategies for regeneration and repair,
and for understanding how urothelial differentiation can go wrong.

## Key facts

- **NIH application ID:** 10187550
- **Project number:** 5R01DK095044-09
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** CATHY Lee MENDELSOHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $506,061
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187550

## Citation

> US National Institutes of Health, RePORTER application 10187550, Retinoic acid signaling controls urothelial development and regeneration. (5R01DK095044-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10187550. Licensed CC0.

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