The pathophysiology of Peyronie's disease: beyond the Smith's space

Graziottin, Túlio M.

doi:10.1590/s1677-5538.ibju.2015.06.02

Cited by 9 publications

(14 citation statements)

References 8 publications

(9 reference statements)

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“…Peyronie's disease is commonly believed to occur as a result of repetitive trauma and buckling of the tunica albuginea during intercourse 96 . Two leading theories concerning the onset of Peyronie's disease are commonly referred to in the scientific literature 6,96,147 . The first theory suggests that trauma separates the inner and outer layer of tunica albuginea, preferentially at the dorsomedial aspect of the penis where the inner layer forms the intercavernous septum.…”

Section: Peyronie's Diseasementioning

confidence: 99%

The mechanisms and potential of stem cell therapy for penile fibrosis

2018

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| Fibrosis is often caused by chronic tissue injury leading to a persisting inflammatory response with excessive accumulation of extracellular connective tissue proteins. Peyronie's disease, urethral stricture and penile (corpora cavernosa) fibrosis are localized fibrotic disorders of the penile connective tissues that can substantially impair a patient's quality of life. Research over the past few decades has revealed the ability of stem cells to secrete a wide range of paracrine factors, a characteristic that could be exploited therapeutically to prevent and treat several inflammatory and fibrotic diseases. In preclinical studies, mesenchymal stem cells (MSCs) have proven to be the most effective and readily available type of stem cells for therapeutic use. An important advantage of MSCs is their ability to circumvent the immune system and function as immunomodulatory 'drug stores' to influence multiple cell types simultaneously. Many studies using stem cells have been applied exclusively to corpora cavernosa fibrosis owing to its well-established disease models. A plethora of preclinical data suggest the benefit of stem cells for use in penile fibrosis. However, their exact mechanism of action and optimal timing and mode of administration must be determined before clinical translation.

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Section: Peyronie's Diseasementioning

confidence: 99%

The mechanisms and potential of stem cell therapy for penile fibrosis

2018

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“…All these processes probably occur between the inner layer of the TA and the vascular, loose, areolar connective tissue sleeve without elastic fibers in Smith space. 57 Bernau et al 58 found that tensin 1 (TNS1) overexpression in primary cultures of human pulmonary fibroblasts contributes to the excessive accumulation of ECM due to the formation of fibrillar adhesions that bind extracellular fibronectin fibrils. The status of hyaluronan/versican complexes within a provisional matrix plays important roles in maintaining many fibrotic conditions and probably also PD.…”

Section: Introductionmentioning

confidence: 99%

New insights into the pathogenesis of Peyronie's disease: A narrative review

Krakhotkin¹,

Chernylovskyi²,

Mottrie

et al. 2020

Chronic Diseases and Translational Medicine

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Peyronie’s disease (PD) is a benign, progressive fibrotic disorder characterized by scar or plaques within the tunica albuginea (TA) of the penis. This study provides new insights into the pathogenesis of PD based on data from different studies regarding the roles of cytokines, cell signaling pathways, biochemical mechanisms, genetic factors responsible for fibrogenesis. A growing body of literature has shown that PD is a chronically impaired, localized, wound healing process within the TA and the Smith space. It is caused by the influence of different pathological stimuli, most often the effects of mechanical stress during sexual intercourse in genetically sensitive individuals with unusual anatomical TA features, imbalanced matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP), and suppressed antioxidant systems during chronic inflammation. Other intracellular signal cascades are activated during fibrosis along with low expression levels of their negative regulators and transforming growth factor-β1 signaling. The development of multikinase agents with minimal side effects that can block several signal cell pathways would significantly improve fibrosis in PD tissues by acting on common downstream mediators.

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“…There are two hypotheses regarding the pathogenesis of PD. The first one states that the tunica albuginea was separated by repeated trauma at the inner and outer layer, especially at the dorsomedial aspect where the intercavernous septum is formed ( Gonzalez-Cadavid and Rajfer, 2005 ; Graziottin, 2015 ). The second hypothesis suggests that this separation might occur between sinusoidal tissue and the inner layer of tunica albuginea, subsequently forming micro hematoma in the connective tissue sleeve between tunica albuginea and corpus cavernosum (Space of Smith) ( Milenkovic et al, 2019b ).…”

Section: Pathophysiologymentioning

confidence: 99%

“…However, the prevalence of PD is likely underestimated due to under-reporting bias from those never seeking treatment ( Chung et al, 2020 ). Although the mechanisms of PD are not fully understood several molecular pathological changes of the PD plaque have been recognized recently ( Graziottin, 2015 ; Paulis et al, 2017 ). Currently, available satisfactory treatments for PD are limited, and in certain situations non-surgical medication might be an important alternative therapeutic approache to PD.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms and Current Pharmacotherapy of Peyronie’s Disease: A Review

2021

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Peyronie’s disease (PD) is a localized fibrotic lesion of the penis that has adverse effects on men’s health. In this review, we summarized the molecular mechanisms and pharmacotherapies of PD. A literature search was conducted using PubMed and Cochrane Library during 2001–2020. Although no oral or topical medication demonstrated efficacy in monotherapy of PD, several intralesional medications have yielded promising results. Currently, the effective strategy in management of PD should be combined modality therapy, including but not limited to pharmacotherapy, mechanical therapy, and psychotherapy. Meanwhile, basic research is still necessary to facilitate the development of novel and more reliable treatments. In future, more attention should be given simultaneously to epigenetic changes, inflammatory cytokines, the abnormal wound-healing process, and profibrotic and anti-fibrotic factors to provide more options for this refractory disease.

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The pathophysiology of Peyronie's disease: beyond the Smith's space

Cited by 9 publications

References 8 publications

The mechanisms and potential of stem cell therapy for penile fibrosis

The mechanisms and potential of stem cell therapy for penile fibrosis

New insights into the pathogenesis of Peyronie's disease: A narrative review

Molecular Mechanisms and Current Pharmacotherapy of Peyronie’s Disease: A Review

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