Characterization of urethral fibrosis in a rabbit model: Potential roles of Wnt-β catenin pathway and epithelial to mesenchymal transition.

Abstract:

AIM:To elucidate the precise cellular and molecular mechanisms that underlie urethral fibrogenesis. METHODS:Endoluminal electrocautery injury (using Karl Storz 10 Fr. Pediatric urethroscope) was employed in male rabbits (n = 6) to create mucosal injury. Retrograde urethrogram (RUG) and endoluminal ultrasound techniques were used to assess severity and changes in luminal cross-sectional area. Six control rabbits were subjected to sham injury, in which the electrocautery was inserted but not powered. Urethral tissues were harvested 30 days postinjury and subjected to RNA sequencing and quantitative polymerase chain reaction (qPCR) to determine changes in gene expression. Histological, immunostaining, and Western blot studies were used to determine changes in protein expression of known markers of fibrosis (eg, collagen, Integrinαv, GIV/Girdin, transforming growth factor-β (TGF-β), and pSMAD1,2,3). RESULTS:Trichrome staining confirmed increased connective tissue in urethral scar tissues. Immunostaining revealed a potential role for epithelial to mesenchymal cell transition (EMT) and positive labeling for all fibrotic markers (eg, collagen-1, Integrin αv, GIV/Girdin, transforming growth factor-β (TGF-β), and SMAD1,2,3). Western blot analysis confirmed increased protein levels of these fibrotic markers. CONCLUSION:Our RNA sequencing and qPCR studies, in conjunction with our protein data, suggest that urethral mucosal fibrogenesis may be mediated by novel fibrogenic signaling pathways involving Wnt-β catenin, TGF-β, GIV/Girdin, and EMT which lead to increased collagen deposition. Therapeutic strategies targeting these pathways may be beneficial in attenuating fibrogenesis and stricture progression.

journal_name

Neurourol Urodyn

authors

Tai JW,Yu H,Chilukuri AT,Bhargava R,Deshpande R,Li W,Ongkeko WM,Bhargava V,Rajasekaran MR

doi

10.1002/nau.24281

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

625-632

issue

2

eissn

0733-2467

issn

1520-6777

journal_volume

39

pub_type

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