HSPA1B Overexpression Induces Benign Prostatic Hyperplasia through Enhancing Endoplasmic Reticulum Stress to Promote NLRP3 Inflammasomes-Mediated Pyroptosis.

The activated pyroptosis participates in the development of benign prostatic hyperplasia (BPH)-related diseases. However, pyroptosis-related mechanism in BPH has not yet been studied, which is the focus of our current study. The potential genes that were abnormally expressed in BPH were predicted by bioinformatics. Human prostate cell lines WPMY-1 and BPH-1 underwent transfection and treatment of endoplasmic reticulum (ER) stress inhibitors 4-phenylbutyric acid (4-PBA) or tauroursodeoxycholic acid (TUDCA), after which the cell viability, lactate dehydrogenase (LDH) activity (cytotoxicity) and pyroptosis were determined through cell counting kit-8 assay, specific kits, and flow cytometry, respectively. Co-immunoprecipitation was performed to detect whether there exists a direct interaction between HSPA1B and CHIP. Quantitative real-time reverse transcription polymerase chain reaction or western blot was applied to assess the involved expressions of genes/proteins. Heat shock protein family A (Hsp70) member 1B (HSPA1B) was highly expressed in BPH. HSPA1B overexpression decreased viability and CHIP expression, and increased pyroptosis, and upregulated expressions of NLR family pyrin domain containing 3 (NLRP3), Pro-caspase-1, Active caspase-1, GDSMD-N, CHOP, p-PERK, PERK and ATF4 in BPH-associated cells; however, shHSPA1B produced opposite effects. CHIP and HSPA1B directly interacted. HSPA1B overexpression enhances viability and reduces cytotoxicity in recipient cells through a paracrine mechanism. TUDCA and 4-PBA counteracted the effects of HSPA1B overexpression on ER stress, viability, LDH activity, and NLRP3 inflammasomes-mediated pyroptosis in BPH-associated cells. Collectively, HSPA1B overexpression induces BPH through enhancing ER stress to promote NLRP3 inflammasomes-mediated pyroptosis, implying that HSPA1B can be a promising target of pyroptosis in BPH therapy.