Upregulated Interleukin 21 Receptor Enhances Proliferation and Epithelial-Mesenchymal Transition Process in Benign Prostatic Hyperplasia

Abstract

Background: Interleukins (ILs) and related chronic inflammation have been found to contribute to the development of benign prostatic hyperplasia (BPH) in recent decades. As a late member of the ILs family, IL-21 receptor (IL-21R) can modulate cell proliferation, however, IL-21R activity in the prostate has not been examined. The current study aimed to elucidate a potential role of IL-21R in the development of BPH.Material and Methods: Human prostate tissues, cell lines and rats were used. QRT-PCR, Western blot, and immunohistochemistry, along with hematoxylin and eosin, Masson's trichrome, and immunofluorescent staining were performed. BPH-1 cells with IL-21R silenced were cultured or co-cultured with macrophages (active THP-1, AcTHP-1). Apoptosis and cell cycle phases were determined via flow cytometry. Epithelial-mesenchymal transition (EMT) processes were also examined. In vivo, rat prostatitis was induced with intraprostatic injected lipopolysaccharide (LPS).Results: IL-21R was highly expressed in human as well as rat prostate, mainly in the epithelial compartment. BPH concomitant with prostatitis significantly upregulated the expression of IL-21R. Knockdown of IL-21R induced cell apoptosis and cycle arrest at G0/G1 phase, and blocked the EMT process in BPH-1 cells. When IL-21R silenced BPH-1 cells were co-cultured with AcTHP-1 cells, these aforementioned processes and IL-21R change were completely reversed. Prostatic hyperplasia was observed with IL-21R upregulated in LPS induced prostatitis rats. More specifically, the expression of apoptosis, cyclin, and EMT proteins in this rat model are altered in a manner consistent with that seen in the cell line model.Conclusions: Our novel data demonstrates the expression and functional activities of IL-21R in the mechanism for development of BPH. IL-21R mainly localized in prostate epithelium and it was upregulated in hyperplastic prostate tissues. IL-21R enhanced proliferation of BPH-1 cells, via inhibiting cell apoptosis, and modulating cell cycles, as well as the EMT process, in response to inflammatory stimuli.

Efficacy and Safety Evaluation of Transurethral Resection of the Prostate versus Plasmakinetic Enucleation of the Prostate in the Treatment of Massive Benign Prostatic Hyperplasia

“…Surgical treatment is the preferred treatment for poor drug treatment efficiency. The most commonly used surgical method is TURP, which has ever been considered the gold standard [7][8][9]. BPH is treated with TURP with high-frequency electric and heat energy.…”

Curcumin attenuates prostatic hyperplasia caused by inflammation via up-regulation of bone morphogenetic protein and activin membrane-bound inhibitor

“…Clinical trials have shown that curcumin can alleviate the inflammatory response with no side effects in patients with BPH who underwent transurethral resection of the prostate (Cosentino et al 2016). In addition, considering that EMT is an inevitable process in the occurrence and development of BPH (Lu et al 2012;Shao et al 2014;Xu et al 2019), we selected curcumin, a drug that has both anti-inflammatory and anti-EMT properties, for the present study.…”

“…As previously reported by Xu et al (2019), a BPH mouse model was established after intraprostatic injection of LPS. As shown in Figure 1(A), the size of the mouse prostate in the LPS group was notably larger than that in the control group.…”

M2a macrophage can rescue proliferation and gene expression of benign prostate hyperplasia epithelial and stroma cells from insulin‐like growth factor 1 knockdown

“…Cell lines obtained and cultured, flow cytometry analyses, MTT assays, quantitative real‐time polymerase chain reaction (qRT‐PCR), Western blot analysis, and immunofluorescent staining were performed as we previously described 25 …”

“…Human prostate samples were collected as we previously described 25 . Prostate samples from five young brain dead men (mean age, 28.4 ± 4.5 years old) proceeding organ donation were regarded as controls and samples from 10 elderly male patients (mean age, 70.1 ± 5.6 years old) undergoing radical resection for bladder cancer were regarded as BPH groups.…”