骨关节炎滑膜uPA,uPAR,tPA表达及意义

目的:探讨尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)和组织型纤溶酶原激活物(tPA)在OA的发生发展中的意义.方法:采用免疫组化方法检测滑膜组织中uPA,uPAR,tPA的表达.结果:40例OA滑膜中阳性表达uPA 31例(77.5%)、uPAR 22例(55%)、tPA 37例(92.5%).10例对照滑膜中阳性表达uPA 2例(20%)、uPAR 1例(10%)、tPA 8例(80%).阳性表达主要分布在滑膜衬里层细胞.结论:uPA系统可能参与介导软骨降解.促进OA的发生发展;而tPA可能与OA关系不密切.     

骨关节炎滑膜uPA,uPAR,tPA表达及意义

目的：探讨尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)和组织型纤溶酶原激活物(tPA)在OA的发生发展中的意义。方法：采用免疫组化方法检测滑膜组织中uPA，uPAR，tPA的表达。结果：40例OA滑膜中阳性表达uPA31例(77．5％)、uPAR22例(55％)、tPA37例(92．5％)。10例对照滑膜中阳性表达uPA2例(20％)、uPAR1例(10％)、tPA8例(80％)。阳性表达主要分布在滑膜衬里层细胞。结论：uPA系统可能参与介导软骨降解。促进OA的发生发展；而tPA可能与OA关系不密切。     

基质金属蛋白酶9及TGF-β1 mRNA和蛋白在骨关节炎中的表达

目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0.01)。实验组MMP-9 mRNA与蛋白表达成正相关(r=0.924,P=0.000),TGF-β1 mRNA及蛋白表达亦成正相关(r=0.941,P=0.000);实验组MMP-9及TGF-β1蛋白表达成负相关(r=—0.762,P=0.000),MMP-9 mRNA及TGF-β1 mRNA表达成负相关(r=?0.681,P=0.000)。结论 OA中TGF-β1的高表达下调了关节软骨与滑膜中MMP-9的表达,对OA关节软骨起保护作用,从而延缓OA进展。     

基质金属蛋白酶9及TGF-β_1 mRNA和蛋白在骨关节炎中的表达

目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0....     

SH关节腔内注射治疗兔膝关节炎的实验研究

[目的]探讨透明质酸钠（sodium hyaluronate，SH）关节腔内注射治疗膝骨性关节炎（OA）的效果。[方法]24只兔子建立骨关节炎动物模型，随机分OA组、SH组、对照组，观察3组软骨、滑膜细胞病理切片及软骨MMP-1免疫组化，进行软骨Mankin＇s评分，以及检测血液和关节液的IL-1含量的效果。[结果]SH组可见软骨破坏减轻，滑膜纤维增生减少，Mankin＇s评分有明显改善（P〈0．05）；血、膝关节滑液IL-1浓度降低（P〈0．05），但关节软骨中MMP表达仍然活跃。[结论]SH能减少滑液中炎性介质IL-1的分泌，从而减轻滑膜炎症，缓解对软骨细胞的破坏，延缓OA进展，但仍阻止不了OA进展。     

凋亡相关基因Bax和bcl-2在骨关节炎软骨中的作用

目的探讨原发性骨关节炎与继发性骨关节炎发病机制的异同。方法收集原发性骨关节炎、继发性骨关节炎的关节软骨各8例，并以9例正常关节软骨作对照，采用RT—PCR和免疫组化方法分别检测Bax和bcl-2的mRNA和蛋白的表达，应用细胞核荧光染色的方法进行软骨细胞凋亡的检测。结果1．原发性骨关节炎组BaxmRNA表达明显升高，与继发组、对照组差异均有统计学意义（P〈0．01，P〈0．01），而继发性骨关节炎组Bax mRNA的表达与对照组之间的差异没有统计学意义（P〉0．05）；bcl-2mRNA在两类骨关节炎中的表达较对照组均升高（P〈0．01，P〈0．05），而两组间差异没有统计学意义（P〉0．05）。2．免疫组化发现两类骨关节炎中Bax、bcl-2蛋白表达水平与其mRNA表达相一致。3．原发性骨关节炎组、继发性骨关节炎组和正常对照组细胞凋亡率分别为10％～20％，8％～13％，2％～5％。原发性骨关节炎组细胞凋亡比例最高。结论软骨细胞凋亡是骨关节炎发病的重要原因，受Bax和bcl-2的共同调节；Bax表达水平的升高可能是原发性骨关节炎发病的重要原因。     

5氟脲嘧啶关节腔注射治疗兔膝骨性关节炎的实验研究

[目的]评价5氟脲嘧啶（5-Fluorouracil，5Fu）关节腔注射治疗兔膝骨性关节炎（osteoarthritis，OA）的疗效。[方法]24只兔子制成骨关节炎模型随机分成OA组、5Fu组和对照组，OA组立即处死，5Fu组按5Fu2ms／kg关节腔注射，每周1次连续4次，对照组注射等量生理盐水，最后1次治疗后1周处死。观察3组滑膜组织的光镜、电镜改变及软骨的光镜、MMP-1免疫组化改变，比较软骨Mankin＇s评分及关节液中IL-1的浓度。[结果]5Fu组可见软骨破坏减轻，滑膜炎症明显抑制，Mankin’s评分明显改善（P〈0．01）；关节液IL-1浓度降低（P〈0．05），关节软骨中MMP-1表达减弱。[结论]5Fu关节腔内注射能抑制滑膜炎症，缓解软骨的破坏。     

尿激酶型纤溶酶原激活因子及其受体在神经母细胞瘤中的表达及其意义

目的：研究尿激酶型纤溶酶原活因子（uPA)及其受体（uPAR）在神经母细胞瘤（NB）中的表达和意义。方法：应用免疫组织化学方法研究uPA及uPAR在42例神经母细胞瘤中的表达，并应用逆转录-聚合酶链式反应（RT－PCR）方法检测患儿骨髓和外周血中的神经蛋白基因产物9．5（PGP9．5）。结果：uPA及uPAR阳性表达主在进展期肿瘤（均为85．7％）高于局灶期肿瘤（42．9％，28．6％）；预后不良型患儿（91．7％，83．3％）高于预后良好型患儿（均为44．4％），且差异均具有非常显著性（P＜0．01）。患儿骨髓和外周血中PGP9．5阳性检出率在uPA阳性患儿组（60．0％）显著高于uPA阴性患儿组（8．3％，P＜0．01）；uPAR阳性组（57．1％）高于uPAR阴性组（21．4％，P＜0．05）。uPA和uPAR同时阳性的10例患儿，骨髓和外周血中均有PGP9．5阳性表达，而同时阴性的5例患儿中，均未检测到PGP9．5。结论：uPA和uPAR在NB的浸润转移过程中发挥重要的作用。     

黄芪对人肾小管上皮细胞细胞外基质分泌的影响及其机制探讨

目的：探讨黄芪对人肾小管上皮细胞细胞外基质分泌的影响及甚可能机制。方法：将体外培养的人肾小管上皮（HK-2）细胞株转板至细胞融合并同步后,分为空白对照组、转化生长因子-β（TGF-β1）刺激组（5ng／ml）、TGF-β1加黄芪100μg／ml组、TGF-β1加黄芪1mg／ml组。作用24h后半定量逆转录多聚酶链反应（RT—PCR）检测纤维连接蛋白（FN）及纤溶酶原激活物抑制剂-1（PAI-1）mRNA;酶联免疫吸附试验（ELISA）法检测上清液中FN的含量;westernblot检测PAI-1的表达。结果：（1）HK-2细胞表达少量FN和PAI-1;（2）HK-2细胞在5ng／ml TGF-β1．刺激下分泌FN、PAI—1mRNA及FN、PAI-1蛋白表达明显增加,与空白对照组比较差异有统计学意义（P〈0．01）;（3）HK-2细胞在TGF-β1和不同浓度的黄芪作用后,可使FN、PAI-1mRNA及蛋白表达减少,与TGF-β1组比较差异有统计学意义（P〈0．01）,尤以黄芪1mg／mi组为甚。结论：TGF—β1可促进HK-2细胞分泌FN和PAI—1,黄芪可部分拮抗TGF-β1的上述效应。这可能是黄芪预防或改善肾小管间质病变的作用机制之一。     

骨关节炎软骨细胞凋亡调控基因的研究

目的　比较分析正常人及老年性骨关节炎患者软骨细胞bax和bcl 2的表达及细胞凋亡状况。　方法　取 9例骨关节炎患者的关节软骨做实验标本 ,以 6例无骨关节炎病史的意外死亡者关节软骨作为正常对照 ;采用逆转录 /聚合酶链反应 (RT PCR)方法检测bax和bcl 2mRNA表达 ,免疫组化检测bax和bcl 2蛋白 ;应用TUNEL方法进行凋亡细胞原位检测。　结果　骨关节炎患者和正常对照软骨细胞都能表达bax和bcl 2mRNA ;骨关节炎关节软骨细胞baxmRNA表达量较正常对照显著增高 (P <0 0 1) ,bcl 2mRNA表达量也高于正常对照组 (P <0 0 5 ) ,两组间bax/bcl 2表达量的比值差异无显著性意义 (P >0 0 5 ) ;免疫组化可检测到相应表达水平的蛋白 ;骨关节炎软骨细胞凋亡 (4%～ 14% )多于正常对照 (0～ 2 % )。　结论　软骨细胞凋亡受bax和bcl 2共同调节 ;bax和bcl 2的共同调节结果可能是OA患者软骨细胞凋亡增加 ,但凋亡率不高、病理过程进展缓慢的一个重要的原因     

Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitors in patients with renal cell carcinoma: correlation with tumor associated macrophage and prognosis

PURPOSE: Urokinase-type plasminogen activator (uPA) has an important role in tumor progression through the degradation of extracellular matrix. In addition, uPA receptor (uPAR) and plasminogen activator inhibitors (PAIs), composed of PAI-1 and 2, are also known to affect such activities. Tumor associated macrophage (TAM) is an important regulator of tumor progression that is associated with the uPA system in various cancers. However, to our knowledge the clinical significance of PAI-2 and the relationship between the uPA system and TAM in human renal cell carcinoma (RCC) tissues have not been investigated. We investigated and clarified these issues. MATERIALS AND METHODS: The subjects of the current study were 106 consecutive surgically resected specimens from patients with RCC. The expression of uPA, uPAR, PAI-1 and PAI-2 was determined by immunohistochemistry. We also examined the relationships among these molecules, survival and TAM. RESULTS: The mean immunoreactive scores (range 0 to 6) of uPA, uPAR, PAI-1 and PAI-2 were 3.09, 2.22, 1.99 and 0.56, respectively. These scores correlated with the grade and presence of metastasis. The expression of uPA, uPAR and PAI-1 but not PAI-2 correlated negatively with cause specific survival. Of uPA family members multivariate analysis showed that PAI-1 independently influenced cause specific survival. TAM counts correlated with PAI-1 only (p <0.001). CONCLUSIONS: Our results suggest that PAI-1 is an important regulator of tumor progression and survival, and PAI-1 may modulate them via TAM. On the other hand, PAI-2 has a minimum role in survival. Our results may help discussions of treatment strategy in patients with RCC.     

Expression of urokinase-type plasminogen activator system in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

The objective of this study was to evaluate the expression levels of urokinase-type plasminogen activator (uPA) system in radical prostatectomy (RP) specimens in order to clarify the significance of the uPA system in prostate cancer. Expression levels of uPA, uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 in RP specimens obtained from 153 patients with clinically organ-confined prostate cancer who had not received any neoadjuvant therapies were evaluated by immunohistochemical staining. Various expression levels of uPA, uPAR, PAI-1, and PAI-2 were noted in the majority of prostate cancer specimens. Expression levels of uPA and uPAR were significantly associated with major prognostic indicators, including pathological stage, Gleason score, lymphatic invasion, surgical margin status and lymph node metastasis. However, PAI-1 expression was related to only pathological stage and surgical margin status, and there was no significant association between the expression level of PAI-2 and several parameters examined. Despite the lack of prognostic significance in PAI-2 expression, biochemical recurrence-free survival of patients with strong uPA, uPAR, and PAI-1 expression was significantly lower than that of those with weak uPA, uPAR, and PAI-1 expression, respectively. Furthermore, strong expression of uPA in addition to a Gleason score, positive surgical margin, and lymph node metastasis could be independent predictors for biochemical recurrence after RP. These findings suggest that the uPA system may be involved in the progression of prostate cancer, and that the expression level of uPA in prostate cancer tissue could be used as a useful predictor of biochemical recurrence in patients undergoing RP.     

Association of interleukin-8 and plasminogen activator system in the progression of colorectal cancer

The aim of this study was to investigate the relationship of Interleukin-8 (IL-8) with vascular endothelial growth factor (VEGF) and plasminogen activator system (PA system) in the progression of colorectal cancer (CRC). In eighty-seven patients with CRC, the levels of IL-8, and VEGF as representative angiogenic factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues. The levels of IL-8, VEGF, and PA system factors in tumor tissues were all significantly higher than those in normal tissues. The IL-8 level was significantly associated with tumor size, depth of infiltration, Dukes stage, and liver metastasis, and also significantly correlated with the levels of VEGF, uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor size, vascular involvement. The levels of uPAR and PAI-1 were significantly associated with tumor size and depth of infiltration, and the uPAR level was associated with liver metastasis. The VEGF level was significantly correlated with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA system factors are contributed to tumor growth, invasion, and metastasis in CRC. Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were significantly associated with a shorter overall survival time; however, multivariate analysis identified only liver metastasis as an independent prognostic factor. In conclusion, IL-8 is responsible to tumor progression and liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as VEGF may play an important role in the progression of CRC.     

纤溶酶原激活物抑制物1与肝细胞癌

目的研究纤溶酶原激活物抑制物１（ＰＡＩ１）在肝细胞癌（ＨＣＣ）蛋白和ｍＲＮＡ水平的表达及其与ＨＣＣ生物学特性的关系。方法取ＨＣＣ石蜡标本４８例,肝良性肿瘤石蜡标本１２例（对照组）做免疫组化染色;液氮冻存ＨＣＣ标本２０例,肝血管瘤５例（对照组）做免疫印迹杂交。结果肝癌细胞与癌周细胞及对照组肝细胞相比,ＰＡＩ１抗原蛋白和ｍＲＮＡ表达显著升高,差异有显著意义,Ｐ值分别＜００１和＜０．０５。术后２年内死亡病例与生存病例相比,ＰＡＩ１阳性率有显著意义的升高,Ｐ＜００５。ＰＡＩ１和纤溶酶原激活物（ｕＰＡ）及其受体（ｕＰＡＲ）同时阳性患者与同时阴性患者相比,前者侵袭性病例较后者升高有显著性意义（Ｐ＜００５）。结论ＨＣＣ中ＰＡＩ１蛋白和ｍＲＮＡ表达明显增高。ＰＡＩ１与ＨＣＣ浸润转移和预后密切相关。     

Expression of urokinase plasminogen activator and its receptor during acute renal allograft rejection

BACKGROUND: In inflammation, urokinase plasminogen activator (uPA) and its receptor (uPAR) play an important role in fibrinolysis and in activation and chemotaxis of neutrophils and lymphocytes. Moreover, the uPA/uPAR system is involved in processes that affect turnover of the extracellular matrix (ECM). The aim of this study was to determine the local and systemic release of uPAR, and the expression of uPA and uPAR in renal tissues during acute renal allograft rejection. METHODS: Blood, urine, and tissue samples were collected from 33 patients diagnosed with acute allograft rejection and from 14 transplant patients without rejection. From 10 healthy volunteers, blood and urine were collected as a control. In urine and blood samples, the levels of uPAR were determined by enzyme-linked immunosorbent assay (ELISA). Immunostaining and in situ hybridization for uPA and uPAR were performed on renal biopsies. RESULTS: uPAR was detectable at low levels in serum and urine of healthy volunteers and was increased in nonrejecting allograft recipients. Serum and urine levels of uPAR were higher in transplant recipients with rejection compared to nonrejectors. The urine and serum levels of uPAR correlated with the renal function. Immunostaining and in situ hybridization showed an up-regulation of both uPA and uPAR in rejection biopsies. Nonrejected grafts displayed no expression of uPA and uPAR by immunostaining, or of uPAR by in situ hybridization. uPA was detected in a limited number of tubular epithelial cells by in situ hybridization. During rejection, lymphocytes as well as tubular epithelial cells showed uPA and uPAR expression. In the vascular types of rejection, strong expression of uPA was also seen in the entire vessel wall, while uPAR was expressed by the endothelium. CONCLUSION: This study shows that (1) uPA and uPAR are up-regulated during acute renal allograft rejection; (2) uPAR levels in urine and serum correlate with serum creatinine levels, and (3) uPA and uPAR are produced by inflammatory cells, tubular epithelium, and vascular endothelium during acute renal allograft rejection.     

封闭负压引流技术对创面愈合过程纤溶酶原激活剂级联表达的影响

目的研究封闭负压引流技术对急慢性创面纤溶酶原激活剂(plasminogen activator,PA)级联中尿激酶型纤溶酶激活剂(urokinase-type plaminogen activator,uPA)和尿激酶型纤溶酶激活剂受体(urokinase-type plasminogen activator receptor,uPA)表达的影响。方法雄性小家猪5头,背部两侧形成急性创面,分为实验组和对照组,仅实验组动物接受封闭负压引流治疗。分别在治疗前和治疗后第1、3、6、9、12、18、25天于创缘切取标本,用兔抗人uPA和uPAR单克隆抗体按ABC程序进行免疫组织化学染色,并计算uPAA和uPAR的标记指数。人慢性创面6例,清创后进行持续封闭负压引流治疗,在治疗后第13、、5、7天采集创面渗出液,并用ELISA法检测渗出液中uPA和uPAR的含量。结果猪急性创面在封闭负压引流治疗后uPA和uPAR均增加,在第3天达到高峰,然后急速下降,但实验组的基因表达量和染色强度均显著高于对照组。6例人慢性创面进行治疗前uPA和uPAR表达较多,随着治疗时间的延长而逐渐减少。结论封闭负压引流治疗既能上调急性创面伤口周围的表皮角质形成细胞的uPA和uPAR表达,使之迅速增殖迁移;又能通过抑制慢性创面uPA和uPAR表达,从而减少细胞外基质的降解。     

Transforming growth factor beta1, urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in head and neck squamous carcinoma and normal adjacent mucosa

BACKGROUND: A balance between urokinase-type plasminogen activator (uPA) and its main inhibitor type-1 (PAI-1) appears to be important for cancer invasive behavior. Since uPA/PAI-1 system seems to be regulated by transforming growth factor beta1 (TGFbeta1) in different cell types, our aim was to investigate the relationship between the expression of the three genes and lymph node status in head and neck squamous cell carcinomas (HNSCC) at specific sites. MATERIALS AND METHODS: uPA, PAI-1, and TGFbeta1 mRNAs were determined by Northern analysis in tumor, and paired normal mucosa samples were obtained from 91 operable HNSCC patients. RESULTS: In oral cavity, excluding tongue, TGFbeta1, PAI-1, and uPA mRNAs values were consistently lower in the normal tissues than in tumors. In larynx tumors, TGFbeta1 expression was increased, but no statistically significant differences were found for uPA or PAI-1 mRNAs as compared with normal tissues. Tongue tumors overexpressed only uPA mRNA, and uPA levels showed significant parallel variations with TGFbeta1 and PAI-1 mRNAs mainly in pN+ tumors. In oral cavity tumors, an inverse correlation between TGFbeta1 and uPA was observed in pN0 subgroup, elevated uPA mRNA was counterbalanced by high PAI-1 mRNA TGFbeta1, and PAI-1 were not coordinately expressed. Correlations between the three markers were not found in larynx. Hypopharynx tumors, all staged as pN+, expressed the lowest TGFbeta1 mRNA mean values. CONCLUSIONS: Combined information about TGFbeta1, uPA, and PAI-1 mRNAs may add some clues to the understanding of the pathophysiological role of uPA system in head and neck squamous cell carcinoma.     

Nipple Aspirate Fluid Expression of Urokinase-Type Plasminogen Activator,Plasminogen Activator Inhibitor-1, and Urokinase-Type Plasminogen Activator Receptor Predicts Breast Cancer Diagnosis and Advanced Disease

Background: Tumor expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA receptor (uPAR) are breast cancer prognostic factors. Less is known about their usefulness in breast cancer diagnosis. Nipple aspirate fluid (NAF) is secreted into the breast duct and collected noninvasively, making it potentially useful both in breast cancer diagnosis and prognosis. We determined the association of uPA, PAI-1, and uPAR levels in NAF with breast cancer (1) detection and (2) advanced disease.Methods: A total of 88 NAF specimens were collected from women with or without breast cancer, and uPA, PAI-1, and uPAR expression were measured by enzyme-linked immunosorbent assay.Results: uPA and uPAR were independent predictors of cancer presence; uPAR was also an independent predictor of advanced disease stage. Higher PAI-1 expression in breast cancer that was found with univariate analysis was not observed after logistic regression was applied.Conclusions: NAF evaluation of uPA, uPAR, and, perhaps, PAI-1 (significant only in univariate analysis) may provide useful breast cancer diagnostic and prognostic information.     

Effects of uPA on mesangial matrix changes in the kidney of diabetic rats

Objective: To investigate the effect of urokinase-type plasminogen activator (uPA) on mesangial matrix in the kidney of diabetic rats and its related mechanisms. Methods: Diabetic Sprague-Dawley (SD) rats induced by intraperitoneal injection of streptozotocin (STZ) were randomly and evenly divided into two groups: DM?+?vehicle, and DM?+?uPA (2500?U?kg^?1 uPA via tail vein once a day for four weeks). The normal SD rats without diabetes were considered as control group. Rats in the three groups were executed and the heart blood was sampled for determination of blood glucose and serum creatinine. Meanwhile, kidney tissues of rats were also harvest for measurement of glomerular area, volume, and mesangial area by periodic acid silver methenamine (PASA) staining. The expression of urokinase-type plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and collagen IV in renal tissues was tested with immunohistochemistry. Results: Compared with control, the DM rats had obvious albuminuria, significantly (p?<?0.01) increased glomerular volume and mesangial matrix area, and significantly (p?<?0.05) higher expression of uPAR, PAI-1 and collagen IV in mesangial matrix, significantly up-regulated (p?<?0.05) glomerular uPAR, PAI-1, and collagen IV expression. After treated with uPA, the diabetic rats had significantly (p?<?0.05) reduced albuminuria, significantly (p?<?0.01) improved glomerular volume and mesangial matrix, significantly (p?<?0.05) down-regulated PAI-1 and collagen IV expression in mesangial matrix. However, the uPAR expression in renal tissues were unchangeable (p?>?0.05) and PAI-1 and collagen IV expression were significantly (p?<?0.05) reduced when diabetic rats were treated with uPA. Conclusion: uPA can down-regulate glomerular PAI-1 expression in the DM rats but not significantly influence uPAR expression, suggesting that uPA might regulate the mesangial cell (MC) and its matrix expression and improve diseased diabetic mesangial matrix via its combination with uPAR to uptake PAI-1 and accelerate its degradation.