Dataset Information

Urine miR-21-5p as a potential biomarker for predicting effectiveness of tadalafil in benign prostatic hyperplasia.

ABSTRACT:

Aim

To investigate whether urine levels of miRNAs that regulate the function of endothelial cells are associated with effectiveness in benign prostatic hyperplasia (BPH) patients treated with a phosphodiesterase type 5 inhibitor, tadalafil.

Patients & methods

We measured urine levels of three miRNAs (miR-21-5p, miR-126-5p & miR-155-5p) in 55 BPH patients before and after tadalafil administration to understand its effectiveness.

Results

Baseline urine miR-21-5p level was an independent predictor of response to tadalafil in multivariate regression analysis (odds ratio: 0.28; 95% CI: 0.10-0.77; p = 0.014). Receiver operator curve analysis revealed that baseline urine miR-21-5p could serve as a predictor of response (area under curve: 0.85; 95% CI: 0.75-0.95; p < 0.001).

Conclusion

Urine miR-21-5p could serve as a biomarker in predicting response of tadalafil for BPH.

SUBMITTER: Tanaka T

PROVIDER: S-EPMC6060390 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Urine miR-21-5p as a potential biomarker for predicting effectiveness of tadalafil in benign prostatic hyperplasia.

Tanaka Tomoaki T Minami Akinori A Tashiro Kouichiro K Yoshida Naomasa N Tohda Akira A Yamakoshi Yasuo Y Yasumoto Ryoji R Sugita Shozo S Nakatani Tatsuya T

Future science OA 20180315 6

<h4>Aim</h4>To investigate whether urine levels of miRNAs that regulate the function of endothelial cells are associated with effectiveness in benign prostatic hyperplasia (BPH) patients treated with a phosphodiesterase type 5 inhibitor, tadalafil.<h4>Patients & methods</h4>We measured urine levels of three miRNAs (miR-21-5p, miR-126-5p & miR-155-5p) in 55 BPH patients before and after tadalafil administration to understand its effectiveness.<h4>Results</h4>Baseline urine miR-21-5p level was an ...[more]

PMID: 30057782

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Project description: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.

Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Dataset Information

Urine miR-21-5p as a potential biomarker for predicting effectiveness of tadalafil in benign prostatic hyperplasia.

Aim

Patients & methods

Results

Conclusion

Publications

Urine miR-21-5p as a potential biomarker for predicting effectiveness of tadalafil in benign prostatic hyperplasia.

Similar Datasets

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