CD151、c-Met及整合素α3、α6在胰腺导管腺癌中的表达及其与预后的关系

目的 探讨CD151、c-Met和整合紊α3、α6蛋白在胰腺导管腺癌中的表达及其与预后的关系.方法 用免疫组化法检测71例胰腺导管腺癌及10例正常胰腺组织中CD151、c-Met和整合素α3、α6蛋白的表达,分析它们与临床病理特征及患者预后的关系.结果 CD151、c-Met和整合素α3、α6在71例胰腺导管腺癌组织中的表达阳性率分别为81.69%(58/71)、69.01%(49/71)、69.01%(49/71)和84.51%(60/71),而正常胰腺组织均未表达.CD151和c-Met的表达与肿瘤的TNM分期、淋巴结转移显著相关(P值均<0.05).CD151的表达与c-Met及整合素α3、α6的表达呈正相关(r=0.583,P=0.000;r=0.457;P=0.000;r=0.671;P=0.000).单因素分析显示,CD151、c-Met、整合素α3和α6的表达与预后有关(P值均<0.05).多因素分析表明,CD151、c-Met是患者术后生存时间的独立预后因子.结论 CD151、c-Met及整合素α3、α6在胰腺癌的发展、转移及预后发挥重要作用,CD151、c-Met可考虑作为临床评价胰腺癌生物学行为及评估预后的指标.     

Renal studies provide an insight into cardiac extracellular matrix remodeling during health and disease

The remodeling of a heart ventricle after myocardial infarction involves numerous inflammatory mediators that may trigger a long-lasting and a highly fibrogenic process. Likewise, in the kidney, acute and chronic injuries may lead to abnormal extracellular matrix deposition and eventually lead to the loss of renal function. Major breakthroughs have emerged during the last ten years with respect to the pathophysiology of matrix remodeling. Epithelial and endothelial cells are plastic, and able to engage in epithelial (or endothelial)-to-mesenchymal transition (EMT or EndMT), thus actively contributing to the fibrogenesis. Members of the fibrinolytic system were demonstrated to possess unsuspected properties and interact with receptors and integrins on endothelial and epithelial cells. Finally, a notion that stem cells could integrate into damaged tissue has recently emerged, which likely contributes to the tissue repair. In many aspects, the kidney and the heart share many common injury mechanisms. We envision that some of them will be accessible as common therapeutic targets in the future.     

整合素β3在大鼠腹主动脉瘤中的表达及意义

目的 观察整合素β3在大鼠腹主动脉瘤模型中的表达情况,探讨其在腹主动脉瘤发病中的意义.方法 弹力蛋白酶灌注法构建大鼠腹主动脉瘤模型并测量腹主动脉直径,计算直径扩张度;HE染色观察主动脉病理改变;免疫组织化学技术和实时定量PCR技术分别从蛋白水平和基因水平检测主动脉组织中整合素β3的相对表达量.结果 腹主动脉瘤组主动脉扩张度明显高于生理盐水组和正常组(3.689±0.443比1.175±0.159和1),差异有统计学意义(P＜0.05);HE染色腹主动脉瘤组主动脉结构紊乱并有炎症细胞浸润;免疫组织化学结果显示整合素β3在腹主动脉瘤组、生理盐水组和正常组中的表达分别为0.33±0.07、0.20±0.06和0.19±0.07(P＜0.05);整合素β3mRNA在以上三组的相对表达量为36.23±5.65、1.14±0.30和1,差异有统计学意义(P＜0.05).结论 整合素β3的高表达可能参与腹主动脉瘤的发生发展.     

Cartilage destruction by matrix degradation products

Abstract

The progressive destruction of articular cartilage is one of the hallmarks of osteoarthritis and rheumatoid arthritis. Cartilage degradation is attributed to different classes of catabolic factors, including proinflammatory cytokines, aggrecanases, matrix metalloproteinases, and nitric oxide. Recently, matrix degradation products generated by excessive proteolysis in arthritis have been found to mediate cartilage destruction. These proteolytic fragments activate chondrocytes and synovial fibroblasts via specific cell surface receptors that can stimulate catabolic intracellular signaling pathways, leading to the induction of such catalysts. This review describes the catabolic activities of matrix degradation products, especially fibronectin fragments, and discusses the pathologic implication in cartilage destruction in osteoarthritis and rheumatoid arthritis. Increased levels of these degradation products, found in diseased joints, may stimulate cartilage breakdown by mechanisms of the kind demonstrated in the review.     

In Vitro Analysis of CsA-Induced Hepatotoxicity in HepG2 Cell Line: Oxidative Stress and α2 and β1 Integrin Subunits Expression

Background

Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in α2β1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction.

Objectives

In this study we aimed to identify the cellular mechanisms underlying CsA-induced hepatic injury by investigating the activation patterns of the antioxidant enzymes, using HepG2 as an in vitro model.

Materials and Methods

HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10 μg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea production and 7) α2β1 integrin expression were assayed.

Results

CsA treatment demonstrated a dose dependent increase in intracellular levels of ROS, GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly attenuated in 1 and 10 µg/ml concentrations of CsA. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels increased in CsA treated cells, while urea synthesis was significantly decreased following treatment with higher concentrations of CsA (P<0.05). Significant down-regulation of β1integrin expression was observed in 1 and 10 µg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells.

Conclusions

The observed reduction of α2β1 integrin expression following CsA treatment could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further studies are required to elucidate whether this attenuated expression is due to the direct effect of CsA or caused by overproduction of ROS.     

整合素受体β3亚单位在非酒精性脂肪性肝病肝组织中的表达

目的观察在非酒精性脂肪性肝病(NAFLD)不同疾病状态中整合素受体β3亚单位的表达情况。方法清洁级雄性新西兰白兔30只,随机分成两组,一组饲以正常饮食(n=6),另一组饲以高脂饮食(n=24)。高脂饮食组分别在饲养1、2、3个月时随机处死8只白兔,取肝组织行HE染色和天狼星红染色,根据病理结果计算NAFLD活动度积分(NAS)。Western印迹和实时PCR检测肝组织内整合素受体β3亚单位蛋白和mRNA表达,免疫组织化学检测β3亚单位在肝脏细胞内的表达情况。结果根据病理结果,高脂饮食白兔分成3组:单纯脂肪肝组(n=10)、无纤维化的NASt组(n=6)和伴有纤维化的NASH组(n=8),NAS积分分别为2.43±0.79,5.38±1.30和5.13±1.05。与正常对照组相比,单纯脂肪肝组整合素受体β3亚单位的蛋白和mRNA表达差异无统计学意义,而NASH-组的表达明显增加,并且随着肝纤维化的加重,表达量增加更显著(均P<0.05)。此外,与正常对照组相比,单纯脂肪肝组肝组织内表达整合素受体β3亚单位的细胞无明显增多;而NASH组阳性细胞显著增多(均P<0.05),其中伴有纤维化的NASH组阳性细胞最多;这些阳性细胞主要分布于肝细胞间隙内。结论与正常对照组和单纯脂肪肝组相比,NASH组肝组织内有着更显著的整合素受体β3亚单位的表达,并且表达量随着肝纤维化的出现而进一步增加。     

microRNA-124与糖尿病肾脏疾病

microRNA(miRNA)广泛存在于真核生物体内,参与蛋白质的转录和转录后的调控.miRNA具有高度进化保守性及组织特异性,在生物的生长发育、细胞分化、疾病的发展过程中起作用.miRNA-124是microRNAs家族的重要成员,近年研究显示,miRNA-124能够作用于整合素,进而影响肾脏纤维化进程,可能作用于Rho/Rho相关蛋白激酶信号通路,起到保护肾小球滤过屏障的作用,能够作用于信号转导与转录激活因子3、Toll样受体、磷脂酰肌醇3激酶/蛋白激酶B信号通路调节炎性反应,可能成为糖尿病肾脏疾病诊断和治疗的新靶点.     

奥美沙坦通过减低整合素β5的表达促进心肌肥大的消退

目的研究整合素β5和心肌肥大的关系,比较新型血管紧张素Ⅱ-Ⅰ型受体拮抗剂(ARB)奥美沙坦和血管紧张素转换酶抑制剂(ACEI)替莫普利对心肌肥大的作用.方法雄性脑卒中易感型自发性高血压大鼠(SHRSP)33只,5周龄雄性京都种Wistar(WKY)大鼠11只,随机分为SHRSP空白组,SHRSP的奥美沙坦给药组(10 mg·kg-1·d-1),SHRSP的替莫普利给药组(10 mg·kg-1·d-1),WKY作为对照组.给药6周后,取出心脏称重,制作标本进行病理学检查,检测血管紧张素Ⅱ-1型受体(AT1)以及整合素β5的表达量.结果奥美沙坦和替莫普利的使用使SHRSP的收缩压降低,但奥美沙坦比替莫普利的促心肌肥大消退作用更显著.半定量RT-PCR测定表明,SHRSP的AT1和整合素β5的表达量明显高于WKY,奥美沙坦和替莫普利的使用降低了两者的表达量,奥美沙坦的作用更显著.AT1和整合素β5的表达成正相关关系.结论奥美沙坦在抑制心肌细胞肥大和降低AT1、整合素β5的表达量方面比替莫普利有更多获益.整合素β5的表达受抑参与了心肌肥大的消退.整合素β5在心肌细胞的表达可能受到血管紧张素Ⅱ(AngⅡ)通过AT1受体的调节.     

妊娠早期CD56bright CD16- NK细胞CD49d和CD11b的表达分析

目的  探讨早期妊娠和稽留流产患者外周血CD56brightCD16- NK细胞及蜕膜组织子宫自然杀伤(uNK)细胞中整合素α4（CD49d）和αm (CD11b)的表达。方法  采集18例早期妊娠妇女外周血（其中14例另取蜕膜组织）和9例稽留流产妇女外周血,Ficoll密度梯度离心法分离单个核细胞悬液,流式细胞术检测样本CD56brightCD16- NK细胞中CD49d和CD11b表达。结果  CD49d和CD11b在早期妊娠蜕膜CD56brightCD16- NK细胞表达显著低于早期妊娠妇女外周血CD56brightCD16-NK细胞(P＜0.01);稽留流产患者外周血CD56brightCD16- NK细胞的表达较早期妊娠妇女显著降低(P＜0.05)。结论  CD49d和CD11b可能在妊娠早期uNK细胞的募集中起重要作用,同时也可能参与了正常妊娠的维持。