RESUMO
Voiding dysfunction is the primary clinical manifestation of chronic prostatitis (CP), which is a common urological disease. The present study investigated whether prostate fibrosis was associated with urinary dysfunction in CP and if resveratrol improved urinary dysfunction, and the underlying molecular mechanism. A rat model of CP was established via subcutaneous injections of the pertussisdiphtheriatetanus vaccine, which was followed by treatment with resveratrol. Bladder pressure and volume tests were performed to investigate the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression levels of tryptase, chymase, transforming growth factor (TGF)ß, Wnt and αsmooth muscle actin (αSMA). The results demonstrated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure were increased significantly in the CP group compared with the control group. Mast cell (MC) activation, the activity of TGFß/Wnt/ßcatenin pathways, and the expression levels of tryptase and αSMA in the CP group were increased significantly compared with the control group. Resveratrol treatment significantly reversed these factors. Therefore, the results indicate that MC infiltration may induce prostate fibrosis, which exhibits a close association with urinary dysfunction in CP. Resveratrol may improve fibrosis via the suppression of MC activation and TGFß/Wnt/ßcatenin pathway activities.
Assuntos
Mastócitos/efeitos dos fármacos , Doenças Prostáticas/etiologia , Doenças Prostáticas/patologia , Prostatite/complicações , Estilbenos/farmacologia , Doenças Urológicas/complicações , Animais , Biomarcadores , Doença Crônica , Modelos Animais de Doenças , Fibrose , Humanos , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Doenças Prostáticas/tratamento farmacológico , Doenças Prostáticas/metabolismo , Resveratrol , Fator de Crescimento Transformador beta/metabolismo , Triptases/metabolismo , Via de Sinalização WntRESUMO
AIM: We investigated whether prostate fibrosis was associated with urinary dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary dysfunction and the underlying molecular mechanism. METHODS: Rat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. Bladder pressure and volume tests investigated the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression level of C-kit/SCF and TGF-ß/Wnt/ß-catenin. RESULTS: Compared to the control group, the maximum capacity of the bladder, residual urine volume and maximum voiding pressure, the activity of C-kit/SCF and TGF-ß/Wnt/ß-catenin pathways were increased significantly in the CP group. Resveratrol treatment significantly improved these factors. CONCLUSION: CP induced significantly prostate fibrosis, which exhibits a close relationship with urinary dysfunction. Resveratrol improved fibrosis, which may be associated with the suppression of C-kit/SCF and TGF-ß/Wnt/ß-catenin pathway.
Assuntos
Prostatite/tratamento farmacológico , Estilbenos/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Animais , Doença Crônica , Fibrose , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Prostatite/metabolismo , Prostatite/patologia , Prostatite/fisiopatologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Resveratrol , Fator de Células-Tronco/metabolismo , Estilbenos/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Bexiga Urinária Hiperativa/metabolismo , Bexiga Urinária Hiperativa/patologia , Bexiga Urinária Hiperativa/fisiopatologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismoRESUMO
The regulation mechanism of inflammation inducing prostate carcinogenesis remains largely unknown. Therefore, we investigated the role of the c-kit/SCF pathway, which has been associated with the control of prostate carcinogenesis, in chronic prostatitis (CP) rats and evaluated the anti-prostatitis effect of resveratrol. We performed hemolysin and eosin staining to evaluate the histopathological changes in prostates. Multiple approaches evaluated the expression levels of c-kit, stem cell factor (SCF), Sirt1, and carcinogenesis-associated proteins. The CP group exhibited severe diffuse chronic inflammation. Meanwhile, the prostate cells appeared atypia; the activity of c-kit/SCF was upregulated, and carcinogenesis-associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. In summary, CP could further cause prostate carcinogenesis, which may be associated with activated c-kit/SCF signaling. Resveratrol treatment could improve the progression of CP via the downregulation of c-kit/SCF by activating Sirt1.
Assuntos
Prostatite/tratamento farmacológico , Proteínas Proto-Oncogênicas c-kit/genética , Sirtuína 1/metabolismo , Fator de Células-Tronco/genética , Estilbenos/administração & dosagem , Animais , Progressão da Doença , Regulação para Baixo , Humanos , Masculino , Prostatite/genética , Prostatite/metabolismo , Prostatite/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , Fator de Células-Tronco/metabolismoRESUMO
Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates. Western blotting and immunohistochemical staining examined the expression level of c-kit, stem cell factor (SCF), Sirt1, and cell cycle-associated proteins. The model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Gland lumen diameter was also significantly smaller; the activity of c-kit/SCF in the CP rats was increased significantly compared to the control group. Meanwhile, the cell cycle proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. Dysregulation of cell cycle was involved in the pathological processes of CP, which was improved after resveratrol treatment by the downregulation of c-kit/SCF by activating Sirt1.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Prostatite/tratamento farmacológico , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sirtuína 1/biossíntese , Fator de Células-Tronco/metabolismo , Estilbenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células , Doença Crônica , Vacina contra Difteria, Tétano e Coqueluche , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Imuno-Histoquímica , Masculino , Prostatite/genética , Proteínas Proto-Oncogênicas c-kit/genética , Ratos , Ratos Sprague-Dawley , Resveratrol , Sirtuína 1/genética , Coloração e Rotulagem , Fator de Células-Tronco/genética , Estilbenos/uso terapêuticoRESUMO
Acute kidney injury (AKI) is a common clinical condition that confers a risk of progression of chronic kidney disease and a high risk of death. The purpose of the current study is to investigate the anti-apoptotic and anti-fibrotic effects of Zhen-Wu-Tang (ZWT) on cisplatin (CIS)-induced renal injury and elucidate the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the PI3K/Akt signaling pathway, transforming growth factor (TGF)-ß and the Wnt/ß-catenin signaling pathway in the positive effects of Zhen-Wu-Tang on the kidneys. Wistar rats were randomly assigned into six groups of 6 rats each as follows: normal control 1; normal control 2; CIS 1 and CIS 2, which received single intraperitoneal injections of CIS (6 mg/kg); CIS+ZWT 4 and CIS+ZWT 10, which received ZWT (1 ml/100 g/day, ig) starting days after the CIS injection for 4 and 10 days, respectively. Hematoxylin-eosin (H&E) staining was performed to identify the amelioration of histopathological changes in the kidneys and apoptosis of the renal proximal tubular cells. Picrosirius red staining was used to evaluate renal fibrosis after ZWT treatment. The relationship between ZWT and the upregulation of Nrf2, phosphorylation of Akt, and the downregulation of TGF-ß and WNT/ß-catenin were determined by Western blotting. At the end of the experiment, serum was isolated from the orbital blood of rats, and blood urea nitrogen (BUN) and creatinine (Cr) levels were measured. The results showed that ZWT restored the histological alterations, aberrant collagen deposition in the kidneys and the BUN and Cr levels that were increased by CIS. Treatment with ZWT reduced the expression levels of TGF-ß and Wnt and increased the expression levels of Nrf2, PI3K and Akt in the CIS-exposed kidney tissues. Furthermore, ZWT downregulated apoptosis and fibrosis by modulating the expression levels of caspase-3, Bax and alpha-smooth muscle actin (α-SMA). In conclusion, this study provides evidence for the anti-fibrotic and anti-apoptotic roles of ZWT in CIS-induced experimental kidney injury.