MicroRNA-29b attenuates fibrosis in a rat model of Peyronie's disease.

Autor: Candido P; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.; Moriah Institute of Science and Education (MISE), Hospital Moriah, Sao Paulo, Brazil., Pimenta R; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.; Department of Immunology and Immunotherapy and Tisch Cancer Institute, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Maluf FC; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.; Department of Urology, University of California San Francisco, San Francisco, California, USA., Chiovatto C; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.; Centro Universitário São Camilo, Sao Paulo, Brazil., Romão P; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Baldavira CM; Department of Pathology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Ghazarian V; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Camargo JA; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Guimarães VR; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Santos GAD; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Silva IA; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Nascimento B; Division of Urology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Sao Paulo, Brazil., Hallak J; Division of Urology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Sao Paulo, Brazil., Capelozzi VL; Department of Pathology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Srougi M; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.; Centro Universitário São Camilo, Sao Paulo, Brazil., Nahas WC; Urology Department, Uro-Oncology Group, University of São Paulo Medical School and Institute of Cancer Estate of São Paulo (ICESP), Sao Paulo, Brazil., Viana NI; Universidade do Estado de Minas Gerais - UEMG, Passos, Brazil., Leite KR; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil., Reis ST; Urology Department, Laboratory of Medical Investigation (LIM55), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil.; Moriah Institute of Science and Education (MISE), Hospital Moriah, Sao Paulo, Brazil.
Jazyk: angličtina
Zdroj: Andrology [Andrology] 2024 Jun 24. Date of Electronic Publication: 2024 Jun 24.
DOI: 10.1111/andr.13672
Abstrakt: Background: Peyronie's disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes.
Objective: We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie's disease.
Material/methods: The study was designed in two phases. To establish an optimal Peyronie's disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages.
Results: The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie's disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p = 0.05) was associated with significantly increased COL1A1 and transforming growth factor β1 genes and proteins (p > 0.05) in the Peyronie's disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor β1 genes and proteins (p < 0.05).
Discussion: The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor β1. This study reveals the therapeutic potential for Peyronie's disease involving molecular targets.
Conclusion: MicroRNA-29b application on the rat's tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie's disease management.
(© 2024 American Society of Andrology and European Academy of Andrology.)
Databáze: MEDLINE
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