Presentation Authors: Jin Song*, Xiang Peng, Sheng Jindong, Yang Yang, Hu Shuai, Jin Jie, Beijing, China, People's Republic of
Introduction: Our previous studies have shown that collagen accumulation in stromal cells could accelerate BPH progression. At the same time, we found that the condition of autophagy was also increased in BPH fibroblast cells. This research mainly investigates that autophagy could influence the progression of BPH through accelerating myofibroblast phenotype, proliferation and suppress its apoptosis in BPH tissues.
Methods: Paraffin-embedded prostate specimens were collected, of which including early-progressed BPH samples (ageâ‰¤50, obtained from patients undergoing transurethral resection of the prostate, TURP), age-matched prostate samples (ageâ‰¤50, acquired from bladder cancer patients who underwent radical cystectomy and prostatectomy) and elderly BPH samples (ageâ‰¥75, obtained from patients undergoing TURP). LC3 protein was assessed by immunohistochemistry in these samples. Î±-smooth muscle actin and collagen I (Myofibroblast phenotype related genes), cleaved-PARP (apoptosis related gene), p62(autophagy related gene) were detected by western blotting (WB) in primary prostatic stromal cell (Prsc 49 and 53) treated with chloroquine (CQ, autophagy inhibitor). After Prsc cells cultured with rapamycin (Rap, autophagy activator) treatment for 3 days, the conditioned media was harvested and used to evaluate the proliferation of Prsc cells. Quantitative PCR was used to identify cytokines secreted by Prsc cells treated with rapamycin.
Results: 1.The expression of LC3 protein was over-expressed in early-progressed BPH patients than the other groups and it was positive correlation with Î±-smooth muscle actin and collagen I. 2. Autophagy inhibitor CQ could suppress the expression of a-smooth muscle actin and collagen I in Prsc cells via AKT and Erk signaling pathways. Furthermore, it promoted the expression of cleaved-PARP protein and p62. 3. The conditioned media (rapamycin to Prsc) could accelerate the proliferation of Prsc53 cell. 4. CCL5, CXCL8, CXCL12, CXCL13, IL-5, IL-17a and FGF6 were increased in Prsc53 cell after treated with rapamycin for 24 hours.
Conclusions: Autophagy may be as an important effector in the progression of benign prostatic hyperplasia through stimulating myofibroblast phenotype, proliferation and its apoptosis.
Source of Funding: National Natural Science Foundation 8177030512