








































Key Words Competing Interests Article Information

Verteporfin, fibrosis, urinary tract, 
inflammation

None declared. Received on October 14, 2021 
Accepted on October 17, 2021

Soc Int Urol J. 2022;3(1):41–43

DOI: 10.48083/GZTK5882

41SIUJ.ORG SIUJ  •  Volume 3, Number 1  •  January 2022

This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2022 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

COMMENTARY

Verteporfin: A Novel Antiproliferative  
Agent for Urinary Tract Fibrosis?

Jas Singh

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, United States

Urinary tract fibrosis following injury, ischemia, or 
chronic inflammation can produce clinically significant 
obstruction, organ dysfunction, and debilitating 
urinary symptoms. Fibrosis is characterized by the 
excessive deposition of extracellular matrix, collagen, 
and glycoproteins by fibroblasts in response to the 
release of pro-fibrotic mediators such as TGF-β by 
macrophages[1]. This scarring often leads to the 
replacement of normal parenchymal tissue with fibrotic 
tissue, resulting in organ dysfunction and failure 
following chronic progression of this process[2]. Efforts 
to minimize fibrosis and scarring have implications for 
improving post-surgical outcome, preventing urinary 
organ dysfunction, and improving patient quality of life.

The objective of this paper is to review the mechanism 
of action of Verteporfin, prior clinical use, and potential 
avenues for urological implementation. Specifically, we 
seek to examine the novel use of this agent in urinary 
tract fibrosis.

The process of wound healing is divided into linear 
but overlapping phases including hemostasis/coagu-
lation, inf lammation, proliferation, and maturation. 
During the proliferation phase, wound contraction 
leads to the activation of tension sensing pathways[3]. 
Yes-associated protein (YAP) along with its transcrip-
tional coactivator, TAZ, are activated and undergo 
translocation into the nucleus. In the nucleus, YAP/TAZ 
promotes the transcription of Engrailed-1 (En1) which 
then stimulates the conversion of En1-lineage-negative 
fibroblasts into En1-lineage-positive fibroblasts. These 
activated fibroblasts then drive the fibrotic response 
leading to increased collagen deposition and increased 
wound tension, thereby driving a positive feedback loop 
of proliferative fibrosis. The importance of the YAP/TAZ 

signaling pathway has also been elucidated in oncogene-
sis as overexpression has been linked to the proliferation 
of tumor cells. YAP is a critical component of the Hippo 
tumor suppressor pathway where it promotes growth 
factor independent proliferation, epithelial mesenchymal 
transition, and suppression of tumor necrosis factor[4].  
As well, YAP overexpression has been linked to poor 
prognosis in some cancers, including urothelial carci-
noma, secondary to its ability to confer resistance to 
cisplatin therapy[5]. Therefore, this molecular target has 
numerous potential clinical implications.

Verteporfin is an inhibitor of the YAP/TAZ pathway, 
whereby it binds to YAP and interferes with its interac-
tion with TAZ, leading to downregulation of YAP and 
the fibrotic response[4]. As of 2000, the only approved 
clinical use of verteporfin by the U.S. Food and Drug 
Administration is as a photosensitizer for photodynamic 
therapy in the treatment of age-related macular degen-
eration. As a photosensitizer, it facilitates mitochondrial 
damage in target tissues through the generation of reac-
tive oxygen species and anti-vascular endothelial growth 
factor (VEGF) activity[6]. However, its anti-tumor activ-
ity has been demonstrated to occur without the require-
ment for light stimulation[7].

Recently, the role of YAP/TAZ activation in renal 
tubulointerstitial inflammation and fibrosis following 
treatment with verteporfin was evaluated. A key compo-
nent of renal fibrosis is release of the cytokine, TGF-β1. 
TGF-β1 is a potent mediator of fibrosis and therefore 
provides a critical therapeutic target for preventing the 
progression of renal fibrosis following acute kidney 
injury and subsequent chronic kidney disease devel-
opment. Jin et al. investigated the effect of vertepor-
fin on unilateral ureteral obstruction (UUO)-induced 

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renal fibrosis. They found that verteporfin treatment of 
kidneys with UUO showed decreased levels of tubular 
dilation, inflammatory cell infiltration, and tubulointer-
stitial fibrosis compared with controls. As well, vertepor-
fin treated kidneys with UUO exhibited an attenuated 
response with respect to α-smooth muscle actin and 
fibroblast specific protein-1 expression, which are 
central to renal fibroblast activation. Finally, the amount 
of type I collagen expression was reduced significantly in 
kidneys treated with verteporfin[8].

The anti-fibrotic activity of verteporfin has also been 
studied in relation to combination usage with triamcin-
olone acetonide, a corticosteroid with anti-angiogenic 
and anti-fibrotic properties mediated by the inhibition 
of proinflammatory prostaglandins and leukotrienes. 
Ophthalmological studies demonstrated a synergistic 
effect of verteporfin and triamcinolone acetonide[9]. 
Triamcinolone acetonide has been utilized in the treat-
ment of urethral stricture disease and vesicourethral 
anastomotic stenosis, following incisional urethrotomy. 
As well, it maintains clinical applications in the manage-
ment of pathologic phimosis and refractory interstitial 
cystitis. It may be that verteporfin is as efficacious as 
corticosteroids (or more so) for these indications, while 
avoiding the potentially serious adverse side effects.

Outside the urinary tract but within the scope of the 
genitourinary system, verteporfin has been evaluated in 
patients with Peyronie’s disease. Mohede et al. treated 
biopsies of Peyronie’s disease plaques obtained from  
5 patients at the time of surgery with verteporfin and 
then examined the tissue by immunofluorescent stain-
ing for myofibroblast activity. Verteporfin was shown 

to reduce the expression of type I and IV collagen, 
fibronectin (component of the extracellular matrix), 
and LOXL2 and PLOD2, enzymes involved in collagen 
cross-linking which occurs during scar contraction. 
The reduced expression of PLOD2 leads to a softer scar, 
which in turn is more readily degraded by matrix metal-
loproteinases[10].

At present, verteporfin is approved for clinical use 
only in the photodynamic therapy of age-related macu-
lar degeneration; however, the potential applications 
of this agent extend far beyond ocular disease, given 
its regulatory role in the YAP/TAZ signaling pathway. 
Preclinical studies have provided early data regarding 
its use in the urological domain, both as an anti-tu-
mor agent and in the attenuation of renal interstitial 
and Peyronie’s disease fibrosis. Fibrosis and scarring 
can occur anywhere along the urinary tract leading to 
pain, infection, and obstruction, necessitating chronic 
indwelling stent and catheter placement. Attempts to 
mitigate scarring and prevent organ dysfunction and 
failure are paramount in mitigating increasing morbid-
ity and mortality in patients. There may be a role for 
verteporfin treatment of urinary tract fibrosis and scar-
ring both in the primary prevention and secondary 
treatment setting. To answer these questions, additional 
studies are required to evaluate the effect of verteporfin 
on fibrotic strictures obtained from the urinary tract 
including the ureters, bladder, and urethra. If the atten-
uation and prevention of scar formation can be demon-
strated on a preclinical basis, then perhaps verteporfin 
may prove a formidable antiproliferative option for the 
treatment and prevention of urinary tract fibrosis.

42 SIUJ  •  Volume 3, Number 1  •  January 2022 SIUJ.ORG

 COMMENTARY

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43SIUJ.ORG SIUJ  •  Volume 3, Number 1  •  January 2022

A Rare Case of Hypersensitivity Reaction Associated With Sacral Neuromodulation Hardware

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