白细胞介素23受体、白细胞介素17A在炎症性肠病患者中的表达及临床意义

目的：通过检测白细胞介素23受体（1L-23R）及白细胞介素17A（IL-17A）在炎症性肠病（IBD）患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义。方法：收集32例克罗恩病（CD）患者、29例溃疡性结肠炎（UC）患者及27例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-23R、IL-17AmRNA的表达情况,免疫组化技术分析IL-23R、IL-17A在肠黏膜中的原位表达。结果：与健康对照组相比,CD及UC患者肠黏膜组织内IL-23RmRNA表达显著增高（P〈0．05）,CD及UC组间的表达量差异无统计学意义（P〉0．05）。CD及UC患者肠黏膜组织内IL-17AmRNA表达显著增高（P〈0．05）,CD组肠黏膜组织内IL．17AmRNA表达显著高于uc组（P〈0．05）。免疫组化分析显示IL-23R阳性细胞在CD与uc肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-23R蛋白表达量最著增高（P〈0．05）,UC及CD组间的表达量差异无统计学意义（P〉0．05）。IL-17A阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-17A蛋白表达量最著增高（P〈0．05）。结论：IL．23R及IL-17A在IBD患者肠黏膜中表达显著增高,提示IL-23R及IL-17A表达异常与IBD的发生发展密切相关,有可能成为IBD治疗的新靶点。     

白细胞介素23受体、白细胞介素17A在炎症性肠病患者中的表达 及临床意义

目的:通过检测白细胞介素23受体(IL-23R)及白细胞介素17A(IL-17A)在炎症性肠病(IBD)患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义。方法:收集32例克罗恩病(CD)患者、29例溃疡性结肠炎(UC)患者及27例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-23R、IL-17AmRNA的表达情况,免疫组化技术分析IL-23R、IL-17A在肠黏膜中的原位表达。结果:与健康对照组相比,CD及UC患者肠黏膜组织内IL-23R mRNA表达显著增高(P<0.05),CD及UC组间的表达量差异无统计学意义(P>0.05)。CD及UC患者肠黏膜组织内IL-17A mRNA表达显著增高(P<0.05),CD组肠黏膜组织内IL-17AmRNA表达显著高于UC组(P<0.05)。免疫组化分析显示IL-23R阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-23R蛋白表达量最著增高(P<0.05),UC及CD组间的表达量差异无统计学意义(P>0.05)。IL-17A阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-17A蛋白表达量最著增高(P<0.05)。结论:IL-23R及IL-17A在IBD患者肠黏膜中表达显著增高,提示IL-23R及IL-17A表达异常与IBD的发生发展密切相关,有可能成为IBD治疗的新靶点。     

SHIP在炎症性肠病结肠组织中的表达及其临床意义

目的：观察SHIP 在溃疡性结肠炎(UC)和克罗恩病(CD)患者结肠组织标本中的表达情况,探讨其在炎症性肠病发生过程中 所起的作用及意义。方法：收集活动期UC患者,活动期CD 患者,及结直肠癌旁正常粘膜组织（NC组）标本各20 例。将活检标本 进行苏木精- 伊红染色及SHIP 免疫组化染色观察;利用Western blot 半定量比较分析SHIP 蛋白表达及组间差异;Real-time RT-PCR 分析SHIP在RNA水平的表达情况和组间差异。统计学处理采用Student''s t检验。结果：免疫组化染色示UC组SHIP阳 性表达积分为（7.20± 2.53）,CD 组积分为（6.50± 2.76）,对照组积分为（1.10± 0.74）。t 检验组间比较UC组和CD组无统计学差异 (t=0.59,P＞0.05);而UC组与NC组（t=7.32,P＜0.05）,CD组与NC组（t=5.98, P＜0.05）,差异均有统计学意义。Western blot 检测 结肠组织SHIP表达,UC组SHIP 相对表达量为（0.314± 0.021）,CD组（0.301± 0.019）,NC 组（0.163± 0.027）。UC和CD组表达 无差异(t=1.44,P＞0.05),而UC组,CD组与NC 组相比表达明显升高（t=13.88、13.16, P均＜0.05）。Real-time RT PCR 检测UC 组 结肠粘膜SHIP mRNA相对表达量为（0.649± 0.028）,CD 组为（0.645± 0.021）,NC 组为（0.140± 0.015）。同样,UC组与CD 组没 有统计学差异,而其相较对照组表达均升高（P＜0.05）。结论：炎症性肠病患者结肠组织SHIP 表达明显高于正常结肠组织,但其在 溃疡性结肠炎和克罗恩病间没有明显差异;提示SHIP可能在炎症性肠病的发病中发挥重要作用。     

HIF-1alpha和COX-2在溃疡性结肠炎患者外周血及黏膜组织中表达及意义

目的：探讨HIF-1琢和COX-2 在溃疡性结肠炎（UC）患者外周血及黏膜组织中表达及意义。方法：87 例UC患者根据临床病 情分为活动期（n=63）和缓解期（n=24），同期选取行结肠镜检查无异常健康者40 名作为对照组，利用qRT-PCR 对外周血及黏膜 组织标本中HIF-1alpha和COX-2 表达进行检测。结果：活动期UC 患者外周血和黏膜组织中HIF-1alpha mRNA和COX-2 mRNA相对表 达量均高于缓解期患者，且均高于对照组，差异均有统计学意义（P<0.05）；活动期UC 患者中，临床病情重型患者外周血及黏膜组 织中HIF-1-alpha mRNA 和COX-2 mRNA 相对表达量高于中型及轻型患者，差异均有统计学意义（P<0.05），内镜表现分级Ⅲ 级患者 外周血及黏膜组织中HIF-1-alpha mRNA和COX-2 mRNA相对表达量高于Ⅱ级及Ⅰ级患者，差异均有统计学意义（P<0.05）；Pearson 相关分析显示，活动期UC患者外周血及黏膜组织中HIF-1alphamRNA和COX-2 mRNA相对表达量均与Mayo 评分呈正相关（r=0. 592、0.722 和0.694、0.456，P<0.05）；Spearman 相关分析显示，活动期UC 患者外周血及黏膜组织中HIF-1-mRNA 和COX-2 mRNA 相对表达量均与临床病情呈正相关（r=0.804、0.826 和0.752、0.763，P<0.05），且与内镜表现分级呈正相关（r=0.803、0.749和 0.858、0.793，P<0.05）。结论：HIF-1-alpha 和COX-2 在UC患者外周血及黏膜组织中呈高表达，且与患者病情严重程度有关。     

HIF-1α和COX-2在溃疡性结肠炎患者外周血及黏膜组织中表达及意义

目的:探讨HIF-1α和COX-2在溃疡性结肠炎(UC)患者外周血及黏膜组织中表达及意义。方法:87例UC患者根据临床病情分为活动期(n=63)和缓解期(n=24),同期选取行结肠镜检查无异常健康者40名作为对照组,利用qRT-PCR对外周血及黏膜组织标本中HIF-1α和COX-2表达进行检测。结果:活动期UC患者外周血和黏膜组织中HIF-1αmRNA和COX-2mRNA相对表达量均高于缓解期患者,且均高于对照组,差异均有统计学意义(P0.05);活动期UC患者中,临床病情重型患者外周血及黏膜组织中HIF-1αmRNA和COX-2mRNA相对表达量高于中型及轻型患者,差异均有统计学意义(P0.05),内镜表现分级Ⅲ级患者外周血及黏膜组织中HIF-1αmRNA和COX-2mRNA相对表达量高于Ⅱ级及Ⅰ级患者,差异均有统计学意义(P0.05);Pearson相关分析显示,活动期UC患者外周血及黏膜组织中HIF-1αmRNA和COX-2mRNA相对表达量均与Mayo评分呈正相关(r=0.592、0.722和0.694、0.456,P0.05);Spearman相关分析显示,活动期UC患者外周血及黏膜组织中HIF-1αmRNA和COX-2mRNA相对表达量均与临床病情呈正相关(r=0.804、0.826和0.752、0.763,P0.05),且与内镜表现分级呈正相关(r=0.803、0.749和0.858、0.793,P0.05)。结论:HIF-1α和COX-2在UC患者外周血及黏膜组织中呈高表达,且与患者病情严重程度有关。     

IL-23、IL-12在克罗恩病肠粘膜的表达及意义

目的:探讨克罗恩病患者结肠粘膜组织中IL-23、IL-12的表达及其与疾病严重程度的相关性.方法:选取中南大学湘雅医院2005年4月-2011年3月经确诊的30例克罗恩病患者手术标本,对照选取30例结肠癌患者手术切除之正常结肠组织.实验设CD病变肠段组、CD正常肠段组及对照组3组.用免疫组织化学方法检测结肠内IL-12、IL-23的表达,分析IL-23、IL-12的表达与CD的疾病临床严重程度(CDAI)和内镜下肠黏膜损伤程度(CDEIS)的相关性.结果:IL-12的表达:CD病变肠段组、CD正常肠段组、对照组阳性率无统计学意义(P值＞0.05).IL-23的表达:CD病变肠段组阳性率高于CD正常肠段组,CD正常肠段组高于对照组,差异均有统计学意义(P值＜0.05).结论:IL-12在CD患者肠粘膜中不升高,而IL-23在CD表达明显升高,提示IL-23在CD粘膜免疫损伤中发挥一定作用,对CD的诊断有一定的参考价值.     

IgG型浆细胞在溃疡性结肠炎小鼠蛋白C系统变化中的作用

本文旨在探讨IgG型浆细胞在溃疡性结肠炎(ulcerative colitis,UC)小鼠蛋白C系统(protein C system,PCS)变化中的作用。利用4%硫酸葡聚糖钠(dextran sulfate sodium,DSS)模拟小鼠UC,免疫荧光法观察结肠组织黏膜固有层浆细胞及免疫复合物IgA/M/G的类型,分离小鼠结肠组织黏膜固有层细胞,用抗CD38~+、CD54~+抗体双标、流式细胞术检测浆细胞数量,以抗IgA/M/G抗体标记,流式细胞术检测浆细胞类型;模拟IgG型免疫复合物刺激分离培养的巨噬细胞,ELISA法检测上清中促炎细胞因子TNF-α和IL-6的变化;流式细胞术检测TNF-α、IL-6对结肠黏膜微血管内皮细胞蛋白C受体(endothelial protein C receptor,EPCR)、血栓调节蛋白(thrombomodulin,TM)表达的影响,发色底物法检测TNF-α、IL-6对微血管内皮细胞激活的蛋白C(activated protein C,APC)活性的影响。结果显示:与对照组相比,DSS组小鼠结肠组织大量IgG型浆细胞浸润(P0.05),黏膜固有层IgG型免疫复合物水平显著升高;分离培养的巨噬细胞与模拟IgG型免疫复合物共孵育后,上清中炎性细胞因子TNF-α和IL-6明显增高(P0.01);同时TNF-α或IL-6与小鼠结肠黏膜微血管内皮细胞共孵育后,内皮细胞表达EPCR、TM的能力均有所降低(P0.05或P0.01),其APC活性明显降低(P0.05或P0.01)。以上结果提示,UC时IgG型浆细胞数量增加,并通过形成免疫复合物,从而影响巨噬细胞分泌促炎细胞因子,进而影响血管内皮细胞功能,抑制PCS。浆细胞有望成为治疗UC的新靶点。     

Runx3在溃疡性结肠炎中的表达

目的:观察Runx3在溃疡性结肠炎(UC)粘膜组织中的表达,探讨抑癌基因RUNX3在溃疡性结肠炎发病机制中的调控作用.方法:选取经过临床表现、内镜、病理等方法共同确诊的溃疡性结肠炎活检的石蜡标本和结肠癌手术切除标本残端的正常组织石蜡标本,用免疫组织化学的方法检测Runx3蛋白在68例UC及50例对照结肠粘膜组织中的表达情况.结果:Runx3在UC及对照组结肠粘膜组织中均有表达,两者之间的差异无统计学意义(P＞0.05). Runx3的表达与UC患者的性别、年龄及病变严重程度之间无显著性相关(P＞0.05).结论:Runx3作为一个转录因子在溃疡性结肠炎的发病机制中可能通过非直接的方式发挥其重要作用.     

人慢性胃炎粘膜内CD3+细胞,S-100+树突状细胞和nNOS表达的意义

采用免疫细胞化学方法探讨胃粘膜内CD3+细胞,S-100+树突状细胞和nNOS的表达与慢性胃炎的关系及意义.检测标本均取自胃窦部活检的胃粘膜组织.结果显示CD3+细胞主要分布于粘膜上皮、腺上皮和固有膜内,而S-100+树突状细胞则主要位于固有膜内,正常组与浅表性胃炎组和萎缩性胃炎组,浅表性胃炎组与萎缩性胃炎组细胞数量有显著性差异( P<0.01),nNOS阳性反应主要位于粘膜上皮和腺上皮的基底部,但各组之间nNOS的表达程度不同,特别是萎缩性胃炎与浅表性胃炎有显著性差异(P<0.01),我们认为,对CD3+ 细胞,S-100 +树突状细胞和nNOS的检测,不仅有助于判断胃炎的病变程度和临床疗效,而且也为胃炎的治疗提供新的启示.     

CD177~+中性粒细胞在溃疡性结肠炎患者外周血中的表达及临床意义

目的:通过对比CD177~+中性粒细胞在溃疡性结肠炎(UC)患者与正常对照者外周血中的表达差异,分析CD177~+中性粒细胞在溃疡性结肠炎发生发展中的临床意义。方法:收集30例UC患者及20例正常对照者外周血,采用流式细胞术检测中性粒细胞CD177~+中性粒细胞表达情况,对比两组CD177表达差异。结果:UC患者外周血中CD177~+中性粒细胞表达明显高于正常对照组(P 0. 01),中度活动UC外周血CD177~+中性粒细胞表达较轻度者明显增高(P 0. 05),UC患者外周血CD177~+中性粒细胞%与Mayo评分呈显著正相关(r=0. 384,P=0. 036)。结论:CD177~+中性粒细胞在UC患者外周血表达明显增高,且与疾病活动程度密切相关,能够反映UC患者临床疾病活动程度。     

前列腺癌微环境中树突状细胞与各类血细胞的关系及其临床预后价值的研究

探讨前列腺癌微环境中DCs与各类血细胞的关系及临床预后价值.选取16例良性前列腺增生和42例前列腺癌患者的前列腺组织作为研究对象,以S-100、CD83、CD208抗体作为不同状态的DC标记物进行MaxVision法免疫组化染色和Masson染色.采用图像分析软件进行图像处理,其统计数据与患者外周血细胞计数进行统计学分析.S-100、CD83阳性细胞计数和胶原蛋白含量在前列腺增生组较前列腺癌组高(P<0.05).CD208阳性细胞计数在前列腺增生组和前列腺癌组无差异(P>0.05).S-100阳性细胞计数与Gleason评分呈负相关关系(r=-0.533,P<0.01).血小板计数在前列腺癌组较前列腺增生组高(P<0.05).单核细胞计数偏高为前列腺癌危险因素(P<0.05).各类型树突状细胞与血小板计数无直线相关关系(P>0.05).外周血各成熟类型细胞与前列腺癌微环境中DCs计数无明显相关关系.S-100标记的树突状细胞计数可能与前列腺癌患者的预后相关.更大量样本的分析有助于证实单核细胞计数与前列腺癌的发病以及S-100标记树突状细胞计数与前列腺癌的预后之间的相关性.     

Tropic 1808基因在大鼠损伤神经组织中的表达

目的观察Tropic 1808基因在大鼠正常和损伤坐骨神经组织中的表达,探讨Tropic 1808基因在周围神经损伤与再生过程中的作用.方法采用地高辛标记的Tropic 1808 cDNA探针、抗大鼠S-100蛋白抗体,以原位杂交和免疫组织化学双重染色法,观察Tropic 1808基因在正常和损伤大鼠坐骨神经组织中的表达.结果免疫组化结果显示,大鼠正常坐骨神经可表达S-100蛋白,但表达量较低;神经损伤后,其远侧端S-100蛋白的表达量明显增加.原位杂交结果显示,大鼠正常坐骨神经组织未见Tropic 1808 mRNA杂交信号;损伤神经的远侧端呈现较强的阳性信号,而且在部分S-100强阳性反应区可见Tropic 1808 mRNA杂交信号.结论 Tropic 1808基因在正常坐骨神经组织中未见表达;坐骨神经损伤后,其远侧端增殖的雪旺氏细胞可表达Tropic 1808 mRNA.提示,Tropic 1808是一种周围神经损伤后特异表达的基因.     

Differentiation of Langerhans Cells from Interdigitating Cells Using CD1a and S-100 Protein Antibodies

The present study shows that Langerhans cells can be differentiated from Interdigitating cells at the light microscopic level. Superficial lymph nodes and skin taken from necropsies and the lymph nodes of dermatopathic lymphadenopathy (DPL) were used for this experiment. Sections of lymph node and skin were embedded using the acetone, methyl benzoate and xylene (AMeX) method and dendritic cells were immunostained with anti S-100 protein antibody (S-100, and OKT-6 (CD1a) using the restaining method. Langerhans cells in the skin were positive for both CD1a and S-100. Dendritic cells positive for both CD1a and S-100, and dendritic cells positive for S-100, but not for CD1a were observed in superficial lymph nodes. In normal superficial lymph nodes, there were more interdigitating cells than Langerhans cells. The majority of the dendritic cells in the DPL were Langerhans cells. We conclude that the S-100 and CD1a positive cells are Langerhans cells, and the S-100 positive-CD1a negative cells are interdigitating cells.     

Differentiation of Langerhans Cells from Interdigitating Cells Using CD1a and S-100 Protein Antibodies

The present study shows that Langerhans cells can be differentiated from Interdigitating cells at the light microscopic level. Superficial lymph nodes and skin taken from necropsies and the lymph nodes of dermatopathic lymphadenopathy (DPL) were used for this experiment. Sections of lymph node and skin were embedded using the acetone, methyl benzoate and xylene (AMeX) method and dendritic cells were immunostained with anti S-100 protein antibody (S-100, and OKT-6 (CD1a) using the restaining method. Langerhans cells in the skin were positive for both CD1a and S-100. Dendritic cells positive for both CD1a and S-100, and dendritic cells positive for S-100, but not for CD1a were observed in superficial lymph nodes. In normal superficial lymph nodes, there were more interdigitating cells than Langerhans cells. The majority of the dendritic cells in the DPL were Langerhans cells. We conclude that the S-100 and CD1a positive cells are Langerhans cells, and the S-100 positive-CD1a negative cells are interdigitating cells.     

Expression of heat shock protein 32 (hemoxygenase-1) in the normal and inflamed human stomach and colon: an immunohistochemical study

Heat shock protein 32 (Hsp32, hemoxygenase-1) is induced by reactive oxygen metabolites (ROM) and degrades heme leading to the formation of antioxidant bilirubin. Increased mucosal generation of ROM occurs in gastritis and inflammatory bowel disease. We aimed to assess mucosal expression of Hsp32 in normal stomach and colon and to test the hypothesis that disease-related differential expression occurs in inflamed tissue. Gastric body and antral mucosal biopsies were obtained from 33 patients comprising Helicobacter pylori-negative normal controls (n = 8), H pylori-negative gastritis patients (n = 11), and H pylori-positive gastritis patients (n = 14). Forty-seven archival colonic mucosal biopsies selected comprised normal histology (n = 10), active ulcerative colitis (UC) (n = 9), inactive UC (n = 8), active Crohn's disease (CD) (n = 8), inactive CD (n = 6), and other colitides (n = 6). Hsp32 expression in formalin-fixed sections was assessed by avidin-biotin peroxidase immunohistochemistry using a polyclonal rabbit anti-Hsp32 as the primary antibody. Immunohistochemical staining identified Hsp32 in all groups. Diffuse cytoplasmic staining was seen in gastric and colonic epithelial and lamina proprial inflammatory cells. Staining scores for Hsp32 were higher in antral H pylori-positive (P = 0.002) and H pylori-negative (P = 0.02) gastritis than in controls and in body H pylori-positive gastritis than in the other 2 groups (P < 0.01). Expression of Hsp32 was increased in active UC compared with inactive disease (P = 0.03) and normal controls (P = 0.02). In conclusion, Hsp32 is expressed constitutively in normal gastric and colonic mucosa, and differential expression occurs in these tissues when they are inflamed. Upregulation of Hsp32 may be an adaptive response to protect mucosa from oxidative injury in patients with gastritis and inflammatory bowel disease.     

Expression of Toll-like receptor 2 (TLR2), TLR4, and CD14 in biopsy samples of patients with inflammatory bowel diseases: upregulated expression of TLR2 in terminal ileum of patients with ulcerative colitis.

Dysregulation of innate and adaptive intestinal immune responses to bacterial microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2), TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon samples were obtained by colonoscopy from patients with Crohn's disease (CD), ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and CD14 showed a significant increase in TLR2 expression in the terminal ileum of patients with inactive and active UC against controls. Significant upregulation of TLR4 expression relative to controls was found in the terminal ileum and rectum of UC patients in remission and in the terminal ileum of CD patients with active disease. CD14 expression was upregulated in the terminal ileum of CD patients in remission and with active disease, in the cecum of UC patients in remission and with active disease, and in rectum of UC patients with active disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.     

Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis

Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.     

Identification of Restricted Subsets of Mature microRNA Abnormally Expressed in Inactive Colonic Mucosa of Patients with Inflammatory Bowel Disease

Background

Ulcerative Colitis (UC) and Crohn''s Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes.

Methodology/Findings

Expression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or <0.2 -fold relative to control) were considered when Q-PCR data were analyzed. Two subsets of 14 (UC) and 23 (CD) miRNAs with highly altered expression (5.2->100 -fold and 0.05–0.19 -fold for over- and under- expression, respectively; 0.001<p≤0.05) were identified in quiescent colonic mucosa, 8 being commonly dysregulated in non-inflamed UC and CD (mir-26a,-29a,-29b,-30c,-126*,-127-3p,-196a,-324-3p). Several miRNA genes with dysregulated expression co-localize with acknowledged IBD-susceptibility loci while others, (eg. clustered on 14q32.31), map on chromosomal regions not previously recognized as IBD-susceptibility loci. In addition, in silico clustering analysis identified 5 miRNAs (mir-26a,-29b,-126*,-127-3p,-324-3p) that share coordinated dysregulation of expression both in quiescent and in inflamed colonic mucosa of IBD patients. Six miRNAs displayed significantly distinct alteration of expression in non-inflamed colonic biopsies of UC and CD patients (mir-196b,-199a-3p,-199b-5p,-320a,-150,-223).

Conclusions/Significance

Our study supports miRNAs as crucial players in the onset and/or relapse of inflammation from quiescent mucosal tissues in IBD patients. It allows speculating a role for miRNAs as contributors to IBD susceptibility and suggests that some of the miRNA with altered expression in the quiescent mucosa of IBD patients may define miRNA signatures for UC and CD and help develop new diagnostic biomarkers.