N-acetylcysteine Ameliorates Prostatitis via miR-141 Regulating Keap1/Nrf2 Signaling
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ORIGINAL ARTICLE
N-acetylcysteine Ameliorates Prostatitis via miR-141 Regulating Keap1/Nrf2 Signaling Liang-Liang Wang,1 Yu-Hua Huang,1 Chun-Yin Yan,1 Xue-Dong Wei,1 Jian-Quan Hou,1 Jin-Xian Pu,1 and Jin-Xing Lv2,3
Abstract—Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3′-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/ Nrf2 signaling. KEY WORDS: N-acetylcysteine; chronic prostatitis; miR-141; Keap1; Nrf2.
INTRODUCTION Chronic prostatitis (CP) is a surprisingly common healthcare issue and occurs in 5 to 10 % of the male
Liang-Liang Wang and Yu-Hua Huang contributed equally to this work. 1
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China 2 Reproductive Medicine Center, The First Affiliated Hospital of Soochow University, No.188, Shizi St, Canglang District, Suzhou, Jiangsu 215006, China 3 To whom correspondence should be addressed at Reproductive Medicine Center, The First Affiliated Hospital of Soochow University, No.188, Shizi St, Canglang District, Suzhou, Jiangsu 215006, China. E-mail: [email protected]
population [1]. According to National Institutes of Health (NIH) classification of prostatitis, the current prostatitis includes the following [2, 3]: acute bacterial prostatitis (NIH category I), chronic bacterial prostatitis (NIH category II), chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) (NIH category III), an
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