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

Krakhotkin, D.V.; Chernylovskyi, Volodymyr A.; Mottrie, Alexandre; Greco, Francesco; Bugaev, Ruslan A.

doi:10.1016/j.cdtm.2020.06.001

Cited by 15 publications

(29 citation statements)

References 143 publications

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“…Furthermore, we have detected a significant increase in the microvessel and arteriole density in the contracted M-side of the relapsed clubfoot tissue, which was connected to an increase in pro-angiogenic factors 8 . These pathways are identical with those described in other fibroproliferative and angioproliferative diseases, such as Dupuytren’s contracture and Peyronie’s disease 9 , 10 .…”

Section: Introductionsupporting

confidence: 79%

The possible role of hypoxia in the affected tissue of relapsed clubfoot

Novotný

Eckhardt

Doubková

et al. 2022

Sci Rep

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Our aim was to study the expression of hypoxia-related proteins as a possible regulatory pathway in the contracted side tissue of relapsed clubfoot. We compared the expression of hypoxia-related proteins in the tissue of the contracted (medial) side of relapsed clubfoot, and in the tissue of the non-contracted (lateral) side of relapsed clubfoot. Tissue samples from ten patients were analyzed by immunohistochemistry and image analysis, Real-time PCR and Mass Spectrometry to evaluate the differences in protein composition and gene expression. We found a significant increase in the levels of smooth muscle actin, transforming growth factor-beta, hypoxia-inducible factor 1 alpha, lysyl oxidase, lysyl oxidase-like 2, tenascin C, matrix metalloproteinase-2, matrix metalloproteinase-9, fibronectin, collagen types III and VI, hemoglobin subunit alpha and hemoglobin subunit beta, and an overexpression of ACTA2, FN1, TGFB1, HIF1A and MMP2 genes in the contracted medial side tissue of clubfoot. In the affected tissue, we have identified an increase in the level of hypoxia-related proteins, together with an overexpression of corresponding genes. Our results suggest that the hypoxia-associated pathway is potentially a factor contributing to the etiology of clubfoot relapses, as it stimulates both angioproliferation and fibroproliferation, which are considered to be key factors in the progression and development of relapses.

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Section: Introductionsupporting

confidence: 79%

The possible role of hypoxia in the affected tissue of relapsed clubfoot

Novotný

Eckhardt

Doubková

et al. 2022

Sci Rep

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“…Previous articles investigated the effects of iNOS silencing in mice, thereby confirming its anti-fibrotic effect and highlighting its significance in protecting smooth muscle cells (SMCs) of corpus cavernosum ( Ferrini et al., 2010 ). Depending on animal model, iNOS and hypoxia-inducible factor–1 (HIF-1) were upregulated in PD-like lesions ( Krakhotkin et al, 2020 ). Therefore, inhibiting the expression or the product activity of hypoxia-inducible profibrotic gene may be an exciting supplement to PD treatment in the future.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Identification of Potential Hypoxia-Related Genes Associated With Peyronie’s Disease

et al. 2022

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Hypoxia is one of the most important predisposing conditions for Peyronie’s disease (PD) and the pathogenetic mechanism is yet to be completely elucidated. This study applied bioinformatic approaches to select candidate hypoxia-related genes involved in the pathogenesis of PD. The Gene Expression Omnibus (GEO) data set GSE146500 was introduced to compare the transcriptional profiling between normal and PD samples. The differential expression of hypoxia-related gene was determined with R software. On the selected candidate genes, further functional analyses were applied, including protein–protein interactions (PPIs), gene correlation, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A total of 66 candidate genes (24 candidates overexpressed in PD and 42 showing reduced expression in PD) were distinguished according to the differential expression between human fibroblast cells from normal and PD patients. The interactions among these candidate genes were recognized according to PPI analysis. The functional enrichment analyses revealed the potential modulatory functions of the candidate genes in some major biological processes, especially in glycolysis/gluconeogenesis and carbon metabolism. The findings would facilitate further study on the pathogenesis of PD, which might consequently promote the improvement of clinical strategies against PD.

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“…Previous studies on the iNOS knockout mouse have confirmed the anti-fibrotic role of iNOS and emphasized the importance of iNOS in protecting SMCs in the penile corpora cavernosa ( Ferrini et al, 2010 ). Moreover, an animal study also found that the levels of iNOS and hypoxia-inducible factor-1 (HIF-1) rise in PD-like lesions ( Krakhotkin et al, 2020 ). Thus, the inhibition of profibrotic gene expression or activity might be an exciting addition to PD therapy in future.…”

Section: Molecular Mechanismsmentioning

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

Cited by 15 publications

References 143 publications

The possible role of hypoxia in the affected tissue of relapsed clubfoot

The possible role of hypoxia in the affected tissue of relapsed clubfoot

Bioinformatics-Based Identification of Potential Hypoxia-Related Genes Associated With Peyronie’s Disease

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

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