| Background Benign prostatic hyperplasia(BPH)is a common chronic disease that seriously affects patients’ quality of life.Despite decades of research,the molecular mechanism of BPH remains unclear.Lumican(LUM)is one of the highly differentially expressed genes in BPH,and is highly expressed in human prostate.However,its correlation with BPH has not been studied.Objective The aim of this research is to elucidate the part LUM plays in BPH and its particular mechanism.Methods Human prostate tissue,cultured human prostate cell lines(BPH-1 and WPMY-1)and rats were used in this experiment.Real-time quantitative fluorescent PCR(qRT-PCR),Western-blot and immunofluorescence staining were used to detect the expression and localization of LUM in human prostate.LUM knockdown(KD)and overexpression cell models were established.CCK8 method and flow cytometry were used to detect cell viability and apoptosis rate.Western-blot detected the changes of apoptosis-related proteins.Epithelial-mesenchymal transition(EMT)and fibrosis markers were detected by Western-blot and semi-quantitative immunofluorescence analysis.We also examined the pathways associated with LUM’s influence on prostate cells by Western-blot.Finally,the results of cell experiments were further verified in animals.Results Our results show that LUM is mainly localized in the prostatic stroma and is highly expressed in hyperplastic prostates.In addition,LUM KD can inhibit the growth of prostatic cells and induce cell apoptosis.LUM KD inhibited the expression of EMT and fibrosis markers in prostatic cells.The effect of LUM overexpression was opposite to that of LUM KD.In addition,we found that LUM regulates cell proliferation and apoptosis through the integrin α2β1-ERK1/2 pathway,and promotes EMT and fibrosis through integrin α2β1-Rho A/ROCK1/2.The results were further verified in vivo in rats.Conclusions LUM regulates cell proliferation,epithelial-mesenchymal transition and fibrosis in hyperplastic prostate through integrin α2β1 and its downstream Rho A/ROCK1/2 and ERK1/2 pathways. |
