Role of microRNA in chronic visceral nociception.
Role of microRNA in chronic visceral nociception.
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DOI：
10.1016/j.pain.2012.10.015
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发表时间：
2013-01
期刊：
影响因子：
7.4
通讯作者：
Verne NG
中科院分区：
文献类型：
--
作者：
Zhou Q;Verne NG
慢性骨盆疼痛是一种常见的功能性疾病，在美国导致大量发病率。不幸的是，对慢性盆腔内脏痛的潜在病因的理解是不完整的。诱导骨盆局灶性刺激或损伤的动物模型可能在功能相当的肠和膀胱传入通路中产生交叉致敏。有趣的是，以前的工作表明，慢性盆腔疼痛疾病，如间质性膀胱炎和肠易激综合征，经常重叠，这是由于通过盆腔传入神经会聚的神经串扰[5]。因此，对初级内脏传入神经生理学的更好理解，有助于更好地理解导致盆腔内脏慢性感觉改变状态的机制，如间质性膀胱炎、肠易激综合征和输尿管绞痛[4]。microRNA（miRNAs）是一类长度为21-23个核苷酸的内源性表达的RNA [3]。它们是小的非编码RNA分子，具有与短干扰RNA（siRNA）不同但相关的功能。成熟的miRNA是从70至100个核苷酸的发夹前体miRNA切割的19至25个核苷酸长的分子。单链miRNA通过部分序列同源性与靶mRNA的非翻译区（UTR）结合，并导致翻译或mRNA降解的阻断[1]。在过去的十年中，miRNAs已经成为参与关键生物过程（包括发育、分化、凋亡和增殖）的基因表达的调节剂。通过与蛋白质编码基因的靶mRNA的不完全配对进行调节[12]。最近的研究表明，miRNA通过指导互补mRNA分子的序列特异性降解或通过抑制翻译来调节基因表达[6]。关于疼痛机制，选择的miRNA涉及多种细胞过程，包括神经元可塑性和神经发生、伤害感受器兴奋性、疼痛阈值和慢性疼痛病症[10]。例如，He等人报道阿片耐受性由let-7家族microRNA调节，其靶向μ阿片受体[2]。在他们的研究中，他们使用LNA-let-7抑制剂来降低大脑let-7水平，他们发现这会减弱小鼠的阿片类抗伤害耐受性。因此，let-7家族microRNA在阿片类药物耐受中起着不可或缺的作用。最近，Zhou等人评估了肠易激综合征患者的慢性腹痛和盆腔痛与肠通透性增加[13]，发现结肠组织和血液微泡中miR-29 a表达增加[11]。miR-29 a在GLUL基因的30-UTR中具有互补位点，其导致肠易激综合征患者中谷氨酰胺合成酶水平降低、肠通透性增加和慢性内脏痛。在体外抑制miR-29 a表达恢复了肠通透性[11]。因此，肠通透性过高是IBS患者内脏高敏感性和慢性腹部/盆腔疼痛的促成因素[13]。研究慢性膀胱疼痛中miRNA的先驱研究之一评估了miRNA在慢性膀胱疼痛综合征中下调神经激肽-1受体的作用[7]。这项研究表明，增加的miR-328，miR-320，miR-449 b和miR-500表达直接下调膀胱疼痛患者膀胱活检组织中的NK 1 R。通过增加miRNAs表达调节NK 1受体可能是膀胱疼痛综合征的分子机制的基础。在当前的Pain杂志上，Sengupta等人测试了......
Chronic pelvic pain is a common functional disorder that leads to substantial morbidity in the United States. Unfortunately, an understanding of the underlying etiologies of chronic visceral pain in the pelvis is incomplete. Animal models that induce a focal irritative or injury to the pelvis may produce a cross-sensitization in functionally comparable afferent pathways of the bowel and bladder. Interestingly, previous work has shown that chronic pelvic pain disorders, such as interstitial cystitis and irritable bowel syndrome, often overlap as a result of neural cross-talk via the convergence of pelvic afferents [5]. Thus, a better understanding of the physiology of primary visceral afferents has led to better understanding of the mechanisms that lead to states of chronic altered sensations from the pelvic viscera such as interstitial cystitis, irritable bowel syndrome, and ureteric colic [4]. MicroRNAs (miRNAs) are a class endogenously expressed RNA’s 21-23 nucleotides long,[3]. They are small, non-coding RNA molecules, with a function distinct from but related to that of short interfering RNAs (siRNAs). Mature miRNAs are 19-to 25-nucleotide-long molecules cleaved from 70-to 100-nucleotide hairpin pre-miRNA precursors. Single-stranded miRNAs bind through partial sequence homology to the 30-untranslated region (UTR) of target mRNAs and cause a block in translation or mRNA degradation [1]. Over the past decade, miRNAs have emerged as regulators involved in gene expression of critical biological processes, including development, differentiation, apoptosis and proliferation. The regulation occurs through imperfect pairing with target mRNAs of protein coding genes [12]. Recent work has shown that miRNAs regulate gene expression by directing sequence-specific degradation of complementary mRNA molecules or by repressing translation [6]. With respect to pain mechanisms, select miRNAs have been implicated in multiple cellular processes, including neuronal plasticity and neurogenesis, nociceptor excitability, pain threshold, and chronic pain conditions [10]. He et al. for example, reported that opioid tolerance is regulated by the let-7 family microRNA, which targets the mu opioid receptor [2]. In their study, they used an LNA-let-7 inhibitor to decrease brain let-7 levels, which they found attenuated opioid antinociception tolerance in mice. Thus, the let-7 family microRNA plays an integral role in opioid tolerance. Recently, Zhou et al. evaluated Irritable Bowel Syndrome patients with chronic abdominal and pelvic pain associated with increased intestinal permeability [13] and found increased miR-29a expression in the colon tissues and blood microvesicles [11]. miR-29a has a complementary site in the 30-UTRs of the GLUL gene that leads to decreased glutamine synthetase levels and increased intestinal permeability and chronic visceral pain in Irritable Bowel Syndrome patients. Suppression of miR-29a expression in vitro restored intestinal permeabilty [11]. Therefore, intestinal hyperpermeability is a contributing factor to visceral hypersensitivity and chronic abdominal/pelvic pain in IBS patients [13].One of the pioneer studies to study miRNA in chronic bladder pain evaluated the role of miRNA in down-regulation of the neurokinin-1 receptor in chronic bladder pain syndrome [7]. This study demonstrated that increased miR-328, miR320, miR-449b and miR-500 expression was directly down regulated NK1R in bladder biopsies from bladder pain patients. Modulation of the NK1 receptor by increased expression of miRNAs may underlie the molecular mechanisms of bladder pain syndrome. In the current issue of PAIN, Sengupta et al. tested the hypothesis that …
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DOI：
10.1523/jneurosci.2419-10.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
He Y;Yang C;Kirkmire CM;Wang ZJ
通讯作者：
Wang ZJ
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP
DOI：
10.1073/pnas.0707594105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Place, Robert F.;Li, Long-Cheng;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
24.5
作者：
Zhou Q;Souba WW;Croce CM;Verne GN
通讯作者：
Verne GN
影响因子：
7.4
作者：
Sengupta JN;Pochiraju S;Kannampalli P;Bruckert M;Addya S;Yadav P;Miranda A;Shaker R;Banerjee B
通讯作者：
Banerjee B