Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients.
Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation.
Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway.
Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression.
World journal of urology. 2024 May 18*** epublish ***
Song Jin, Zhanliang Liu, Peng Xiang, Meng Fu, Gang Zhang, Jianxing Li, Yinong Niu
Department of Urology, Beijing Tsinghua Changgung Hospital, Tsinghua University, No. 168, Litang Road, Beijing, 102218, China., Department of Urology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Beijing, 100050, China., Department of Urology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China., Department of Urology, Beijing Tsinghua Changgung Hospital, Tsinghua University, No. 168, Litang Road, Beijing, 102218, China. ., Department of Urology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Beijing, 100050, China. .