The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie’s Disease
Open accessAbstract
Peyronie’s disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway.
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These pathways often interact and crosstalk with each other, amplifying fibrotic processes and tissue remodeling in the penile tissue.
“These pathways often interact and crosstalk with each other, amplifying fibrotic processes and tissue remodeling in the penile tissue.”
From Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets. (2024) · cites this paper as [79]
The Discussion (page unavailable) links several profibrotic factors to fibroblast proliferation and collagen buildup, supporting the claim’s general reference to fibrosis and tissue remodeling. It does not establish that the pathways interact or cross-talk to amplify fibrosis; instead, it suggests that activation of the extrinsic and intrinsic apoptotic pathways may stabilize plaques and halt fibrosis progression. (LLM, conf=0.82)
Experimental — accuracy not yet measuredElevated levels of Bcl-2 prevent the release of cytochrome c from mitochondria, a crucial step in initiating apoptosis.
“Elevated levels of Bcl-2 prevent the release of cytochrome c from mitochondria, a crucial step in initiating apoptosis.”
From Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets. (2024) · cites this paper as [79]
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- Authors
- Loreto, C., La Rocca, G., Anzalone, R., Caltabiano, R., Vespasiani, G., Castorina, S., Ralph, D. J., Cellek, S., Musumeci, G., Giunta, S., Djinovic, R., Basic, D., & Sansalone, S.
- Affiliations
- University of Catania (IT)
- Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, 90100 Palermo, Italy
- University of Palermo (IT)
- University of Rome Tor Vergata (IT)
- University College Hospital (GB)
- Cranfield University (GB)
- Sava Perovic Foundation, Center for Genito-Urinary Reconstructive Surgery, 11000 Belgrade, Serbia
- Clinic of Urology, Clinical Center Nis, 18000 Nis, Serbia
- Corresponding author
- Loreto, Carla
- ORCID
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-10
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC4147380
- OpenAlex
- W1973666710
- Cited by
- 108
- References
- 48
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 14 · 2022: 20 · 2021: 22 · 2020: 15 · 2019: 12 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Keywords
- Peyronie's disease, mitochondrial apoptosis, apoptosis, tunica albuginea, fibrous plaque, Bax, Bcl-2, caspase-3, caspase-9, myofibroblasts, fibroblasts, ossification centers, penile deformity
- MeSH terms
- Adult, Aged, Humans, Male, Middle Aged, Penile Induration, Staining and Labeling, Signal Transduction, Apoptosis, Disease Progression, In Situ Nick-End Labeling, bcl-2-Associated X Protein, Caspase 3, Caspase 9, Young Adult
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