RESUMEN
OBJECTIVES: 5α-reductase inhibitor (5-ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. MATERIALS AND METHODS: Prostate specimens from patients were collected. Insulin-like growth factor 1 (IGF-1), Beclin-1, LC3 levels, was analysed by immunohistochemistry. The role IGF-1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. RESULTS: We demonstrated that IGF-1 expression is down-regulated in prostate fibroblasts after long-term 5-ARI application. A decrease in IGF-1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF-1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long-term 5-ARI application reduces IGF-1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. CONCLUSIONS: Focusing on the autophagy induced by low levels of IGF-1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Próstata/citología , Próstata/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Beclina-1/metabolismo , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Desnudos , Proteínas Asociadas a Microtúbulos/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Receptores Androgénicos/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Objective :To explore changes of serum levels of galectin-3 and pentraxin-3 (PTX-3) in patients with chro-nic heart failure (CHF) and their correlation with prognosis .Methods : A total of 150 CHF patients (CHF group) treated in our hospital and 150 healthy volunteers undergoing physical examination simultaneously (healthy group ) from Jan 2015 to Dec 2015 were enrolled .Serum levels of galectin-3 ,PTX-3 and N-terminal pro brain natriuretic peptide (NT-proBNP) ,left atrial diameter (LAD) ,left ventricular end-diastolic dimension (LVEDd) and left ven-tricular mass index (LVMI) were compared between two groups at enrollment .According to one-year follow-up out-come ,CHF group (12 cases lost ,another 138 cases) was divided into poor prognosis group (n＝36) and good prog-nosis group (n＝102).Spearman linear correlation analysis was used to analyze correlation among serum galectin-3 , PTX-3 levels and poor prognosis of CHF patients .Results :Compared with healthy group ,there were significant rise in serum levels of galectin-3 [ (2-23 ± 0-25) ng／ml vs .(16-61 ± 1-48) ng／ml] ,PTX-3 [ (1-28 ± 0-54) μg／L vs. (3-58 ± 0-52) μg／L] ,NT-proBNP [(223-23 ± 76-28) pg／ml vs.(952-75 ± 85-43) pg／ml] ,LAD ,LVEDd and LV-MI in CHF group , P＝0-001 all.Compared with good prognosis group at enrollment ,there were significant rise in serum levels of galectin-3 [ (18-52 ± 1-91) ng／ml vs.(24-63 ± 2-26) ng／ml] and PTX-3 [ (2-65 ± 0-74) μg／L vs. (3-95 ± 1-05) μg／L] in poor prognosis group , P＝0-001 both .Spearman linear correlation analysis indicated that serum galectin-3 and PTX-3 levels were significant positively correlated with major adverse cardiovascular events in CHF patients ( r＝0-608 ,0-558 , P＝0-001 both).Conclusion :Serum levels of galectin-3 ,PTX-3 and NT-proBNP levels are significant rise and closely related to prognosis of CHF patients ,can be used as auxiliary indexes predicting prognosis and may provide the basis for formulation of target therapy .