SPARC对增生性瘢痕成纤维细胞Ⅰ型胶原蛋白mRNA表达的影响

目的观察富含半胱氨酸的酸性分泌糖蛋白（SPARC）对增生性瘢痕成纤维细胞Ⅰ型胶原蛋白表达的影响。方法用不同浓度重组人SPARC作用于体外培养的增生性瘢痕成纤维细胞（实验组）,并与空白组作对照。用实时荧光定量RT-PCR法检测其Ⅰ型胶原蛋白mRNA表达情况。结果与空白对照组相比,实验组Ⅰ型胶原蛋白mRNA表达明显增高（P〈0．05）。结论SPARC能显著促进增生性瘢痕成纤维细胞Ⅰ型胶原蛋白基因的表达。     

SPARC在胰岛素抵抗发展中作用机制的研究

RT-PCR、Westem印迹、免疫荧光3种方法检测大鼠脂肪中富含半胱氨酸的酸性分泌蛋白(SPARC)mRNA和蛋白的表达.胰岛素抵抗大鼠脂肪中SPARCmRNA和蛋白的表达高于普通大鼠(均P＜0.01),SPARC在胰岛素抵抗发展中可能起到负反馈调节的作用.

Abstract：

RT-PCR, Western blot, and immunofluorescence were used to examine secreted protein acidic and rich in cysteine(SPARC)mRNA and protein expression in adipose tissue of rats. The results showed that the expression levels of SPARC mRNA and protein in adipose tissue of insulin resistant rats were higher than those of the normal ones(all P＜0.01). SPARC may play a role in the negative feedback regulation duning the development of insulin resistance.     

SPARC在db/db小鼠肌肉组织的表达及临床意义的观察

目的 观察db/db(C57BL/KsJ)小鼠肌肉组织中富含半胱氨酸的酸性分泌蛋白(SPARC)mRNA和蛋白质的表达. 方法 选择12周龄的db/db小鼠(db/db组)及与其同窝野生对照型小鼠(NC组)各6只.分别取小腿肌肉组织,RT-PCR方法检测肌肉组织中SPARC基因表达,Western blot测定SPARC目的蛋白表达,免疫荧光染色法对肌肉组织进行染色. 结果 SPARC的mRNA及蛋白质在db/db组肌肉组织的表达明显强于NC组(P＜0.05). 结论 SPARC在db/db小鼠肌肉组织中呈现高表达,可能与IR及糖尿病的发生发展有密切关联.     

卵巢上皮性肿瘤中SPARC的表达及意义

目的 探讨富含半胱氨酸的分泌型酸性蛋白(SPARC)在卵巢上皮性肿瘤中的表达变化及其与卵巢上皮性癌生物学行为的关系.方法 采用组织芯片及免疫组化技术检测20例良性卵巢上皮性肿瘤及63例原发性卵巢上皮性癌组织中的SPARC,同时对蛋白表达进行定位.结果 原发性卵巢上皮性癌中SPARC表达水平为(4.19±2.28)分,明显低于良性卵巢上皮性肿瘤的(8.55±2.48)分,P<0.05.卵巢上皮性癌中Ⅲ～Ⅳ期、低分化、有腹水及大网膜转移时SPARC较低,与对照者相比,P<0.05.16例癌组织细胞核有表达,其余为细胞质表达.结论 SPARC在卵巢上皮性癌中低表达;SPARC可能参与了卵巢上皮性癌的发生、发展、侵袭、转移过程.     

ob／ob小鼠脂肪组织中富含半胱氨酸的酸性分泌蛋白的表达及临床意义

目的观察富含半胱氨酸的酸性分泌蛋白（SPARC）在ob／ob小鼠脂肪组织中的表达情况。方法选择10周龄的ob／ob小鼠（C57BL／6J—Lepob／J）与其同窝野生对照型小鼠各6只,取其腹部皮下脂肪组织,RT-PCR方法检测脂肪组织中SPARC基因的表达,Westernblot法测定sPARC目的蛋白的表达水平,免疫荧光染色法对脂肪组织进行染色观察。结果SPARC在ob／ob小鼠脂肪组织中表达明显升高。结论SPARC在ob／ob小鼠脂肪组织中呈现高表达,可能参与肥胖和糖尿病的发生发展。     

富含半胱氨酸的酸性分泌蛋白在肺癌和肺纤维化中的研究进展

富含半胱氨酸的酸性分泌蛋白(SPARC)可调控细胞基本功能如黏附、增殖和分化,同时也调控生长因子以及细胞外基质(ECM)降解和转化必需的基质金属蛋白酶(MMPs)的表达和活性。在非小细胞肺癌(NSCLC)和特发性肺纤维化(IPF)中,SPARC通过促进微血管改造和ECM中蛋白过度沉积发挥作用。而SPARC在慢性呼吸道疾病如哮喘和慢性阻塞性肺疾病(COPD)中的作用一直不被重视。为此,本文综述了SPARC在NSCLC和IPF中的作用研究,并提出未来应研究SPARC在哮喘和COPD中的作用。     

SPARC表达下调对胶质瘤细胞增殖、迁徙及黏附能力的影响

目的探讨富含半胱氨酸酸性蛋白(SPARC)在胶质瘤发病中的作用机制,为临床治疗提供新的思路。方法运用RNA干扰技术(RNAi)处理胶质瘤细胞株U251,RT-PCR检测SPARC表达情况,其后分别采用MTT法、细胞迁徙及黏附实验评价SPARC-小干扰RNA(siRNA)对U251细胞增殖、迁徙及黏附能力的影响。结果 siR-NA处理后U251细胞SPARC表达明显下调(P<0.05),经SPARC-siRNA培养后U251细胞的增殖、迁徙及黏附能力均明显减弱(P<0.05)。结论 SPARC可通过增强细胞增殖、迁徙及黏附能力而促进胶质瘤的进展,有望成为一个具有肿瘤特异性的基因敲除治疗靶点。     

富含半胱氨酸的酸性分泌蛋白与冠心病危险因素的相关研究

富含半胱氨酸的酸性分泌蛋白（SPARC）是种小分子钙结合糖蛋白,可由多种细胞分泌,由于其能将钙、胶原和矿物质连接在一起,因此又被叫作骨连接素（osteonectin）、基底膜40蛋白（BM-40）。既往研究表明,SPARC 与人类某些常见疾病密切相关,如骨质疏松［1］、关节炎［2］、癌症［3］、肥胖［4］、肿瘤、创伤修复等。近年来,SPARC 与糖尿病相关疾病如2型糖尿病［5-6］、妊娠糖尿病［7］、糖尿病肾病［8］、糖尿病视网膜病变［9］及心脑血管疾病的关系成为临床研究热点。由于糖尿病是冠心病的等危症,许多危险因素均可导致二者发病。我们对 SPARC 与冠心病的危险因素及相关机制作一综述。     

新诊2型糖尿病患者血清 SPARC 水平及其与胰岛素抵抗的关系

目的：观察新诊断2型糖尿病（T2DM）患者血清富含半胱氨酸酸性分泌蛋白（SPARC）水平变化,探讨其与胰岛素抵抗的相关性。方法检测新诊断未治疗的60例T2DM患者（ T2DM组）及50例同期健康体检者（对照组）的血清SPARC、空腹血糖（ FBG）、糖化血红蛋白（ HbA1C ）、空腹胰岛素（ FINS）、血脂及BMI、腰围、臀围、腰臀比（WHR）,计算胰岛素抵抗指数（HOMA-IR）、胰岛β细胞功能指数（HOMA-β）。结果 T2DM组血清SPARC为（19．26±2．07）μg/L ,对照组为（14．75±1．66）μg/L,P＜0．01。线性相关分析,SPARC水平与TG、FBG、HbA1C、HOMA-IR呈明显正相关（r分别为0．35、0．32、0．41、0．38,P均＜0．01）,与HOMA-β、HDL-C呈负相关（r分别为－0．48、－0．34,P均＜0．01）。多因素线性回归分析显示,HbA1C、FBG、HOMA-IR均为血清SPARC的决定因素（回归系数分别为0．624、0．625、0．709,P均＜0．05）。结论新诊断T2DM患者血清SPARC水平升高,且血清SPARC水平与胰岛素抵抗有关。     

富含半胱氨酸的酸性分泌蛋白在人大肠癌、大肠腺瘤的表达及其临床意义

[目的]探讨富含半胱氨酸的酸性分泌蛋白(SPARC)在人大肠癌、大肠腺瘤中的表达及其临床意义。[方法]采用免疫组化SABC法检测65例人大肠癌、32例人大肠腺瘤及29例正常人大肠组织中SPARC的表达。[结果]免疫组化结果显示SPARC在人大肠腺癌细胞及间质细胞均有不同程度表达。大肠癌、大肠腺瘤及正常组织三者之间比较,SPARC在组织腺管细胞中的阳性表达率差异无统计学意义(P0.05),而在间质细胞中的表达率差异显著(P0.05)。另外,在人大肠癌间质细胞中,SPARC的阳性表达率与癌组织分化程度、淋巴结转移与否呈明显相关性(P0.05),而与患者性别、年龄、肿瘤部位无关(P0.05)。[结论]SPARC有可能作为评估大肠肿瘤浸润转移及其预后的生物学指标,为进一步研究大肠肿瘤的早期筛查与诊断提供了新的思路与方法。     

Secreted protein acidic and rich in cysteine (SPARC) gene polymorphism association with hepatocellular carcinoma in Italian patients

Background and Aim: Hepatocellular carcinoma (HCC) is a multifactorial disease driven by both genetic and epigenetic factors. Infection, inflammation and the immune response against hepatitis B virus and hepatitis C virus have been shown to play an important role in increasing cancer risk and promoting tumor development. In order to investigate the genetic component influencing HCC development, we analyzed 50 single nucleotide polymorphisms (SNP) spanning 34 different genes in 230 Italian patients affected by HCC and 230 controls. Methods: Genes were selected on the basis of their known biological function and their possible involvement in the progression or in the susceptibility to HCC was considered. SNP genotyping was performed using allelic‐specific fluorescent probes. Results: For most SNP, no differences were identified between HCC patients and controls, with the exception of rs2304052, localized on the secreted protein acidic and rich in cysteine (SPARC) gene, which was significantly associated to the disease. The C allele was significantly more frequent in the HCC patients than in the healthy controls (23% vs 10%, corrected P < 0.001), as well as the CC genotype (13% vs 1%, corrected P < 0.001). Conclusion: Since the presence of the rs2304052 C allele is associated with an increased risk (odds ratio: 2.76) of developing hepatocarcinoma, our results allowed us to identify a SNP in the SPARC gene correlating to HCC susceptibility.     

Expression of peritumoral SPARC during distal cholangiocarcinoma progression and correlation with outcome

Abstract

Objectives: Distal cholangiocarcinoma (dCCA) is a malignancy with a dismal prognosis. One of the hallmarks is the presence of a rich desmoplastic stroma believed to contribute to tumor progression and treatment resistance. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in tumor-stroma interaction with prognostic correlation across several malignancies. The aim of the present study was to evaluate the expression pattern and prognostic significance of SPARC in resected dCCA and paired lymph node metastasis.

Materials and methods: SPARC expression was evaluated in 59 resected dCCA samples and 25 paired lymph node metastases as well as 10 benign bile duct samples using immunohistochemistry. Stromal SPARC expression was scored semi quantitatively. Survival was estimated using the Kaplan–Meier method with associated log-rank test.

Results: SPARC expression was absent in normal bile ducts. In dCCA, peritumoral stromal SPARC was detectable in 47/59 (80%) of samples with 40/59 (68%) classified as high stromal SPARC expression. There was a significantly lower proportion of SPARC positive stroma in paired lymph node metastasis 17/25 (68%) than the corresponding primary tumors 24/25 (96%) (p?=?.016). Stromal SPARC expression was associated with the presence of lymph node metastasis; high SPARC expression 31/40 (78%) versus low SPARC expression 9/19 (47%) (p?=?.013). In the present material there was no significant association between stromal SPARC expression and survival.

Conclusions: Stromal SPARC expression occurs frequently in dCCA. Although significantly lower than in primary tumors stromal SPARC is frequently retained in paired lymph node metastasis suggesting a possible role in the metastatic process of dCCA.     

The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone

Background

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential.

重组人PTH(1-34)与依降钙素对绝经后女性骨质疏松患者骨代谢和血清SPARC的影响

目的 观察重组人甲状旁腺素(1-34)[ rhPTH(1-34)]和依降钙素对绝经后女性骨质疏松患者骨密度和骨代谢及血清富含半胱氨酸的酸性蛋白( SPARC)水平的影响.方法 124例绝经后女性骨质疏松症患者随机分为PTH组(n=89),给予rhPTH (1-34)200 U皮下注射每日一次和CT组(n=35),给予依降钙素20U肌肉注射每周一次,共12个月.于治疗前、治疗后6个月、12个月测定各组一般生化指标,腰椎L2-4、左股骨颈、大转子及Ward三角的骨密度、血清钙、磷水平.采用酶联免疫法(ELISA)测定血清骨碱性磷酸酶(BSAP)、富含半胱氨酸的酸性蛋白(SPARC)等骨代谢相关指标水平情况.结果 rhPTH治疗12个月后腰椎L2-4骨密度较基线增加了7.9％(P＜0.05);血清钙和BSAP水平12个月时较治疗前分别增加了8.3％和93.4％(均P＜0.05);血清SPARC水平12个月时较基线增加了12.6％(P＜0.05);与治疗前相比,依降钙素治疗12个月时腰椎L2-4骨密度增加了3.2％(P＜0.05);血清钙、BSAP和SPARC水平均无显著改变.结论 rhPTH (1-34)能显著促进骨合成代谢,其疗效优于依降钙素;血清SPARC水平的增加可能在rhPTH促进成骨过程中起重要作用.     

SFRP1在卵巢癌淋巴结定向高转移细胞中的表达及意义

目的进一步探讨分泌型卷曲相关蛋白（SFRP1在卵巢癌发生、发展中的作用。方法采用荧光定量PCR法定量分析SFRPImRNA在不同淋巴结转移能力卵巢癌Skov3细胞亚系中表达水平。结果SFRPImRNA在原代Skov3细胞与转移能力依次增高的Skov3-pn2、Skov3-pm3、Skov3-pm4细胞系中的表达呈下降趋势（P〈0．05）。结论SFRP1在高淋巴结转移能力的卵巢癌细胞中表达减少，与卵巢癌发生、发展密切相关，其可作为监测卵巢癌的分子靶标。