Journal article
Validation and testing of an in vitro model to study medical treatments for anterior urethral stricture disease: assessing the potential efficacy of phosphodiesterase-4 (PDE4) inhibition and testosterone
Urology (Ridgewood, N.J.)
08/06/2026
DOI: 10.1016/j.urology.2026.07.042
PMID: 42562275
Abstract
To 1) determine the expression and distribution of all PDE4 isozymes (A-D) along the anterior urethra, 2) culture fibroblasts and epithelial cells from healthy and strictured urethras, 3) investigate an in vitro model of anterior urethral stricture disease (aUSD), and 4) assess the therapeutic potential of phosphodiesterase-4 (PDE4) inhibitors and testosterone compared to paclitaxel.
The presence and relative abundance of PDE4 isozymes (A-D) was confirmed using immunohistochemistry on 5 male cadaveric urethras. Human urethral fibroblasts (FBs) were cultured from healthy control urethras of patients undergoing vaginoplasty (n=3) and from idiopathic bulbar urethral strictures (L2S1E2) of patients undergoing urethroplasty (n=3). Epithelial cells (ECs) were cultured from a healthy control urethra and two urethral strictures. To investigate a model of aUSD, Control FBs were stimulated with TGFβ1 and compared to Stricture FBs on assays of cell proliferation and expression of genes relevant to aUSD pathophysiology. To test therapeutics, Stricture FBs were treated with the PDE4 inhibitor, roflumilast, testosterone (T), or paclitaxel and compared to Control FBs on the previously mentioned assays and cell viability.
PDE4-A, B, and D were detected along the urethra and did not differ between regions. TGFβ1 altered proliferation and gene expression in a dose-dependent manner. Roflumilast and T preserved cell viability and proliferation and decreased expression of genes positively associated with aUSD.
Urethral FBs and ECs can be cultured from healthy and strictured surgical specimens, enabling in vitro research. PDE4 inhibitors and T may be non-cytotoxic alternatives or additions to paclitaxel for aUSD.
Details
- Title: Subtitle
- Validation and testing of an in vitro model to study medical treatments for anterior urethral stricture disease: assessing the potential efficacy of phosphodiesterase-4 (PDE4) inhibition and testosterone
- Creators
- Lola P Lozano - University of IowaMichael J Volk - University of Illinois Urbana-ChampaignCarly D Miller - University of IowaJane E Berg - University of IowaChantal Allamargot - University of IowaCharles H Schlaepfer - University of UtahJane T Kurtzman - University of UtahM Ben Christensen - University of UtahJeremy B Myers - University of UtahAlexandria M Hertz - University of IowaAmanda R Swanton - University of IowaBudd A Tucker - University of IowaBradley A Erickson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Urology (Ridgewood, N.J.)
- DOI
- 10.1016/j.urology.2026.07.042
- PMID
- 42562275
- NLM abbreviation
- Urology
- ISSN
- 1527-9995
- eISSN
- 1527-9995
- Publisher
- Elsevier
- Language
- English
- Electronic publication date
- 08/06/2026
- Academic Unit
- Core Research Facilities; Neuroscience and Pharmacology; Urology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9985217068402771
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