Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

AIM: To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma (ESCC). METHODS: Beta-catenin mRNA expression level in 40 ESCC patients (28 males and 12 females, age range 38-82 years, median 60 years) was analyzed by real- time PCR. Beta-catenin mRNA expression levels in tumor cells were categorized as weaker (level 1) or equal to or stronger (level 2) than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS: Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis (0.0776 ± 0.0369 vs 0.3413 ± 0.1803, P < 0.001) and deeper tumor invasion (0.0751 ± 0.0356 vs 0.3667 ± 0.1928, P < 0.001), and a poorer survival rate (P = 0.0024) than ESCC with level 1 expression. CONCLUSION: Beta-catenin expression in ESCC is of great importance.

Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

Objective： To investigate the expressions of beta-catenin, protein APC （adenomatous polyposis coil protein）, c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results： The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors （P〈0.01）. The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too（P〈0.05）. The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors （P〈0.05）. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor （P〈0.05）. Conclusion： The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

Disordered beta-catenin expression and E-cadherin/CDH1 promoter methyiation in gastric carcinoma

瞄准：在胃的癌的原子核或膜 / 细胞质调查 beta-catenin 的分发房间，在 E-cadherin 基因甲基化之间的关系和它的表示，和象在预言肿瘤渗入的潜在的分子的标记的 beta-catenin 和 E-cadherin 的角色。方法：胃的癌的 29 个案例，分类同样弥漫、肠的变体，为学习被选择。原子、细胞质的蛋白质被净化， beta-catenin 内容被 ELISA 检测。E-cadherin/CDH1 基因倡导者的 DNA 甲基化被 methylation 特定的 PCR 和 compaired 学习， E-cadherin 表示由免疫组织化学检测了。结果：在胃的癌的 27 种情况中，在原子核和膜 / 细胞质之间的 beta-catenin 内容的比率与 T 分类被相关(r = 0.392， P = 0.043 ) 。意义在 T2 和 T3 组之间是在场的。没有关联以他们的 beta-catenin 分发在弥漫、肠的变体之间被检测。在胃的癌的弥漫的变体的 21 种情况中，在在 CDH1 基因甲醇化物组和甲醇化物得非的组之间的 E-cadherin 表示有差别(29 % 对 71 % ， P = 0.027 ) 。在 CDH1 基因甲基化和 T 分类之间的关联都没被发现，也不是在 E-cadherin 表示之间的意义，肿瘤渗入分级。结论：比较分析原子并且 membrane/cytoplasmic beta-catenin 能预言本地肿瘤渗入。E-cadherin/CDH1 基因甲基化是为它在弥漫的变体的基因沉默的一个重要原因胃的癌。当 E-cadherin 不在时的 CDH1 基因的甲基化是在胃的致癌作用的一个早事件。

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers

AIM: To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters. METHODS: Tumor samples from 163 cases of colorectal cancer (CRC) who had undergone primary colectomy between May,1998 and November,2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density (OSD) and percentage of cells having nuclear localization was counted as nuclear staining density (NSD). Univariate exploration used log-rank test and multivariate survival analysis used Cox's hazard regression model. RESULTS: Beta-catenin immunoreactivity was detected in 161 samples (98.8%),of which 131 cases had nuclear staining. High OSD (≥ 75%),detected in 123 cases (75.5%),was significantly associated with earlier clinical staging (P < 0.01),lower nodal status (P = 0.02),non-metastatic status (P < 0.01) and better differentiation (P = 0.02). Multivariate analysis found that high OSD was independently associated with better survival [Cox's hazard ratio 0.51,95% confidence interval (CI) 0.31-0.83]. Although high NSD (≥ 75%) was correlated with high pre-operative serum CEA (P = 0.03),well differentiation (P < 0.01),and increased staining intensity (P < 0.01),the parameter was not significantly associated with survival. CONCLUSION: Unlike previous reports,the study did not find a predictive value of nuclear beta-catenin in CRC. Instead,the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover,the parameter also independently predicted superior survival.

E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

AIM: To examine the role of E-cadherin and beta- catenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas (EBV-GCs). METHODS: We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients' prognosis and the expressions of these proteins. RESULTS: Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta- catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 95% confidence interval (CI), 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequentlyin EBV-GCs than non-EBV-GCs (odds ratio = 2.23; 95% CI, 0.97-5.09), and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs (P = 0.024). Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis (P < 0.001). Among EBV- GCs, the depth of invasion (P = 0.005), lymph node metastasis (P = 0.004) and an intestinal type by Lauren classification (hazard ratio = 9.47; 95% CI, 2.67-33.6) were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC (hazard ratio = 0.32; 95% CI, 0.11-0.93). CONCLUSION: We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV- GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

Expressions of Beta-catenin,E-cadherin and MMP-7 in Ovarian Epithelial Tumors

Objective： To investigate the expressions of Beta-catenin, E-cadherin and MMP-7 and their implications in ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expressions of Beta-catenin, E-cadherin and MMP-7 in ovarian epithelial tumor in 66 cases. Results： The abnormal expression rate of Beta-catenin in malignant ovarian epithelial tumor was higher than those in borderline and benign epithelial tumors （P〈0.05）. The positive rates of E-cadherin in benign and borderline ovarian epithelial tumors were significantly greater than that in malignant epithelial tumor. The expression rates of MMP-7 in malignant and borderline ovarian epithelial tumors were higher than that in benign epithelial tumor （P〈0.05）. Conclusion： The abnormal expressions of Beta-catenin, E-cadherin and MMP-7 might be used to indicate the malignance transform of ovarian epithelial tumors, but they have no significant correlation with peritoneal dropsy invasion, caul invasion and appendant invasion in ovarian epithelial tumor.

丹酚酸B对创伤后应激障碍模型大鼠认知功能和GSK-3β/β-Catenin信号通路的影响

目的 探讨丹酚酸B(Sal B)是否可通过调节糖原合成酶激酶-3β/β-连环蛋白(GSK-3β/β-Catenin)信号通路改善创伤后应激障碍(PTSD)模型大鼠认知功能。方法 60只大鼠随机分为正常组、PTSD组、Sal B低剂量组(10 mg/kg)、Sal B高剂量组(20 mg/kg)和GSK-3β抑制剂组(30 mg/kg CHIR-99021),每组12只。除正常组外,其余组大鼠采用单一延长应激法构建PTSD大鼠模型。旷场实验、Morris水迷宫实验评估大鼠认知功能;Nissl染色观察海马神经元病理学变化;TUNEL染色检测海马神经元凋亡;Western blot检测海马组织中裂解的胱天蛋白酶3(cleaved caspase-3)、B细胞淋巴瘤基因-2相关X蛋白(Bax)、原癌基因(c-Myc)、细胞周期蛋白D1(Cyclin D1)、总GSK-3β(tGSK-3β)、磷酸化GSK-3β(p-GSK-3β)、总β-Catenin(t-β-Catenin)、磷酸化β-Catenin(p-β-Catenin)蛋白表达。结果与PTSD组比较,Sal B低剂量组、Sal B高剂量组和GSK-3β抑制剂组大鼠爬行格数、站立次数、运动总距离、跨越原平台次数增多,逃避潜伏期、首次跨越原平台时间缩短,海马神经元凋亡率以及海马组织中Bax、cleaved caspase-3、t-GSK-3β、p-β-Catenin蛋白表达水平降低,Cyclin D1、c-Myc、p-GSK-3β、t-β-Catenin蛋白表达水平升高(P<0.05)。结论 Sal B能够减轻PTSD模型大鼠海马神经元凋亡、损伤并可改善其认知功能障碍,抑制GSK-3β/β-Catenin信号通路。

探讨HBV X、TGF-alpha,c-myc及beta-catenin基因与高发区肝癌的相关性

目的 研究HBVX基因、TGF alhpa、c myc、beta catenin等癌变相关基因及 2 49密码子突变的p5 3蛋白在高发区肝细胞癌癌变发生及其恶性表型维持所发挥的作用。方法 以肝癌高发区启东的肝癌细胞株 770 1和 770 3标本作为研究对象 ,以PCR及DNA测序分析方法确定HBVX基因在细胞DNA水平的整合。以RT PCR及Western blot检测HBVX基因的转录与表达。用PCR RFLP方法确定 p5 3基因 2 49密码子的错义突变。应用免疫组织化学法分析TGF alhpa ,c myc ,beta catenin的表达。结果 2株细胞在DNA水平都存在HBVX基因片断的整合 ,但未见完整的转录和蛋白水平表达。序列分析显示 2株细胞的HBVX基因的序列各有特异性 ,并存在 13 0、13 1密码子的热点突变。PCR RFLP分析说明 2个细胞株中p5 3基因 2 49密码子均属野生型。免疫组化显示 2株细胞中TGF alpha ,c myc和beta catenin蛋白均有显著的积累。 结论 本实验的结果显示HBVX基因对这 2株细胞恶性表型的维持并不存在必然的关联 ,而是 1种HBV感染的遗传标志。未见HBVX基因蛋白表达 ,可能由于X基因 3′端缺失变异所致。免疫组化的结果显示TGF alpha ,c myc和beta catenin蛋白的显著积累 ,说明多种癌基因的相互协同 ,可能与肝癌的发生。

Expression of Beta-Catenin and APC Protein in Ovarian Epithelial Tumor and Its Implication

Objective： To investigate the expression of beta-catenin, APC protein and its implication in ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and APC protein in 48 cases of ovarian epithelial tumor. Results： The abnormal expression rates of beta-catenin in ovarian malignant and borderline epithelial tumors were higher than that in benign epithelial tumors. The expression of APC protein in benign epithelial tumors was significantly greater than that in malignant epithelial tumors. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors. Conclusion： Beta-catenin and APC protein have important effect on pathogenesis and development of ovarian epithelial tumors.

Relationship between Expression of beta-catenin and VEGFs(VEGFA,VEGF-C),VEGF Receptors-2(VEGFR-2)in Medulloblastoma

Objective： To investigate the expression of beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGF receptor-2 （VEGFR-2） protein in medulloblastoma. Methods： Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues. Results： The expression rate of beta-catenin, and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue. A significant positive correlation was found between beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 protein in medulloblastoma. Conclusion： There was a correlation between beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 in medulloblastoma, which may play a role in the pathogenesis and development of medulloblastoma.

益气化瘀解毒法对慢性萎缩性胃炎伴异型增生大鼠APC、beta-catenin表达干预的实验研究

胃癌是一个逐步形成的过程，常由胃癌前病变（PLGC）进一步发展而来。胃癌前病变的早诊断和早干预可以阻断其向胃癌的发展。PLGC分为肠上皮化生（IM）和异型增生（Dys）两种，尤其是中重度异型增生。轻度Dys约15％～30％会进展为重度Dys和／或腺癌，而重度Dys的病人有60％～80％发展为胃癌。有效干预PLGC，阻断其向胃癌的发展，对防治胃癌有积极意义。

小鼠毛囊再生与胸腺素β4的促进效应

背景:近年来研究表明,胸腺素β4与毛囊的生长发育和毛发的生长周期有着密切关系,但其作用机制尚不清楚。目的:探讨胸腺素β4通过Wnt信号通路作用于毛囊干细胞对毛囊再生的促进作用。方法:将实验小鼠随机分为低剂量胸腺素β4组、高剂量胸腺素β4组和对照组,使用松香/石蜡混合制剂建立脱毛模型。低剂量胸腺素β4组和高剂量胸腺素β4组给药浓度分别为0.3μg/50μL和3μg/50μL,对照组给予等量PBS,每隔12 h给药1次,均匀涂抹于小鼠脱毛背部。应用大体照相、苏木精-伊红染色、免疫组化及原位杂交技术,观察毛发生长情况,检测不同时间点和不同给药浓度下小鼠毛囊根部细胞β-catenin、LEF-1 mRNA的表达水平。结果与结论:低剂量胸腺素β4组毛发再生速度高于高剂量胸腺素β4组和对照组。苏木精-伊红染色显示在脱毛初期,各组小鼠真皮和皮下脂肪层有一定炎性细胞浸润,9 d时,低剂量胸腺素β4组生长期毛囊数量明显多于高剂量胸腺素β4组和对照组。免疫组织化学和原位杂交结果分别显示β-catenin和LEF-1 mRNA主要表达于毛囊隆突部和外根鞘处细胞的胞浆中,经积分吸光度分析发现低剂量胸腺素β4组阳性细胞数量和染色强度高于高剂量胸腺素β4组和对照组(P<0.05),高剂量胸腺素β4组与对照组间差异无显著性意义。结果显示低剂量的胸腺素β4可以增加部分毛囊外根鞘处细胞内β-catenin和LEF-1 mRNA的表达。胸腺素β4可以促进毛囊再生的机制可能与影响Wnt信号通路有关。

去卵巢大鼠骨髓基质细胞beta-catenin蛋白表达变化观察

目的观察卵巢切除大鼠骨髓基质细胞(BMSC)beta-catenin蛋白表达的变化。方法将18只健康3月龄未经产雌性SD大鼠随机平分为去卵巢和假手术两个组。术后14周,取左侧股骨,新鲜分离骨髓细胞,静置贴壁法体外培养9d后,采用间接免疫荧光方法检测BMSC中beta-catenin蛋白表达和定位的变化。取右侧股骨,在双能直线χ-射线骨密度仪上检测骨密度的变化。结果大鼠去卵巢14周后,股骨近端和远端的骨密度显著下降(P<0.05),而股骨干的骨密度没有变化(P>0.05)。在体外培养的假手术组BMSC中,beta-catenin蛋白主要在胞核中表达。与假手术组相比,去卵巢组BMSC核中beta-catenin蛋白表达减少,而胞膜中表达增加。结论beta-catenin蛋白在卵巢切除大鼠BMSC核中表达的下降可能与绝经后骨质疏松症的发生有关。

Beta-Catenin,APC蛋白,C-myc及CyclinD_1在卵巢上皮肿瘤中的表达及意义

目的:探讨卵巢上皮性肿瘤的beta-catenin,APC蛋白及c-m yc,cyclin D1的表达及意义。方法:采用ABC免疫组织化学染色方法检测48例卵巢上皮性肿瘤(其中包括18例良性肿瘤,13例交界性肿瘤及17例恶性肿瘤)的beta-catenin,APC蛋白,c-myc及cyclinD1的表达。结果:beta-catenin在卵巢恶性上皮肿瘤及交界性上皮肿瘤中异常表达率均明显高于其在卵巢良性上皮性肿瘤中的表达(P<0.001)。抑癌基因APC蛋白在卵巢恶性上皮性肿瘤及交界性上皮肿瘤的表达明显低于卵巢良性上皮性肿瘤(P<0.05)。癌基因c-myc,cyclinD1在卵巢恶性上皮肿瘤及交界性上皮肿瘤中的表达均强于卵巢良性上皮肿瘤(P<0.05)。卵巢上皮性肿瘤中beta-catenin与APC蛋白呈负相关(P<0.05);beta-catenin与c-myc,cyclinD呈正相关(P<0.05)。结论:APC-beta-catenin-Tcf-4通路异常对卵巢上皮肿瘤的发生,发展起重要作用,beta-catenin异常表达可能激活原癌基因C-m yc,cyclin D1的表达。

他莫昔芬联合左炔诺孕酮对大鼠子宫肌瘤的影响及机制研究

目的:探讨他莫昔芬联合左炔诺孕酮对大鼠子宫肌瘤的影响及其作用机制。方法:选择SPF级成年雌性SD大鼠30只,采用苯甲酸雌二醇联合黄体酮腹腔注射建立子宫肌瘤模型。将大鼠随机分为对照组(正常大鼠2 ml 0.9%氯化钠溶液灌胃)、模型组(子宫肌瘤大鼠2 ml 0.9%氯化钠溶液灌胃)、他莫昔芬组(子宫肌瘤大鼠1.70 mg/kg他莫昔芬灌胃)、左炔诺孕酮组(子宫肌瘤大鼠0.1 mg/kg左炔诺孕酮灌胃)和联合组(子宫肌瘤大鼠他莫昔芬联合左炔诺孕酮灌胃),每组6只,连续灌胃30 d。ELISA检测大鼠血清雌二醇(E2)、孕激素、促卵泡激素(FSH)、促黄体生成素(LH)水平。测量子宫系数、左右宫颈角长度及宫角最大直径。HE染色观察子宫组织结构及内膜厚度。Western blot检测子宫组织Wnt5b、β-连环蛋白(β-catenin)蛋白表达。结果:与对照组比较,模型组血清E2、孕激素、FSH、LH水平升高(均P<0.05)。联合组血清E2、孕激素、FSH、LH水平低于他莫昔芬组和左炔诺孕酮组(均P<0.05)。模型组子宫系数、左右宫颈角长度、宫角最大直径及子宫内膜厚度较对照组增加(均P<0.05)。联合组子宫系数、左右宫颈角长度、宫角最大直径及子宫内膜厚度低于他莫昔芬组和左炔诺孕酮组(均P<0.05)。联合组子宫损伤程度较模型组减轻。模型组子宫组织Wnt5b、β-catenin蛋白表达高于对照组(均P<0.05)。联合组Wnt5b、β-catenin蛋白表达低于他莫昔芬组和左炔诺孕酮组(均P<0.05)。结论:他莫昔芬联合左炔诺孕酮能够缩小大鼠子宫肌瘤,改善子宫形态,抑制子宫平滑肌细胞增大,其机制可能与抑制Wnt/β-catenin通路有关。

黄精多糖调控骨髓间充质干细胞向成骨细胞分化

背景:骨髓间充质干细胞具有多向分化潜能。黄精多糖可能通过Wnt/β-catenin信号通路促进小鼠骨髓间充质干细胞的成骨分化。目的:探讨黄精多糖对小鼠骨髓间充质干细胞向成骨细胞分化过程中Wnt/β-catenin信号通路的影响。方法:培养小鼠骨髓间充质干细胞,在传统成骨诱导培养基诱导下给予5,10,25,50 mg/L黄精多糖进行干预,不加黄精多糖作为对照组,显微镜下观察细胞形态变化。PNPP法检测碱性磷酸酶活性;观察细胞发生矿化并进行茜素红染色,记录矿化结节数和面积分数;q RT-PCR检测成骨相关基因碱性磷酸酶、Runx2、骨钙素m RNA表达;采用q RT-PCR和Western Blot分别检测β-catenin基因和蛋白表达水平;采用双荧光素酶报告基因检测系统检测下游β-catenin/TCF的转录活性。结果与结论:(1)与对照组相比,不同质量浓度的黄精多糖以剂量依赖性的方式提高碱性磷酸酶活性(P<0.05),显著增强细胞的矿化能力,明显提高碱性磷酸酶、Runx2、骨钙素基因的表达(P<0.05);(2)诱导后β-catenin m RNA在第3天表达最高,黄精多糖在促进骨髓间充质干细胞向成骨细胞分化的过程中还能显著上调β-catenin的表达(P<0.05),促使含有TCF结合位点的荧光素酶报告基因(TOPFlash)的高表达(P<0.05);(3)说明黄精多糖通过激活Wnt/β-catenin信号通路促进小鼠骨髓间充质干细胞向成骨细胞分化。

Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

AIM:To investigated the molecular cause of very early-onset ulcerative colitis(UC)in an 18-mo-old affected child.METHODS:We analysed the interleukin-10(IL10)receptor genes at the DNA and RNA level in the proband and his relatives.Beta catenin and tumor necrosis factor-α(TNFα)receptors were analysed in the proteins extracted from peripheral blood cells of the proband,his relatives and familial adenomatous polyposis(FAP)and PTEN hamartoma tumor syndrome(PHTS)patients.Samples were also collected from the proband’s inflamed colorectal mucosa and compared to healthy and tumour mucosa collected from a FAP patient and patients affected by sporadic colorectal cancer(CRC).Finally,we examined mesalazine and azathioprine effects on primary fibroblasts stabilised from UC and FAP patients.RESULTS:Our patient was a compound heterozygote for the IL10RB E47K polymorphism,inherited from his father,and for a novel point mutation within the IL10RA promoter(the-413G->T),inherited from his mother.Beta catenin and tumour necrosis factorαreceptors-Ⅰ(TNFRI)protein were both over-expressed in peripheral blood cells of the proband’s relatives more than the proband.However,TNFRII was over-expressed only in the proband.Finally,both TNFα-receptors were shown to be under-expressed in the inflamed colon mucosa and colorectal cancer tissue compared to healthy colon mucosa.Consistent with this observation,mesalazine and azathioprine induced,in primary fibroblasts,IL10RB and TNFRII over-expression and TNFRI and TNFαunder-expression.We suggest thatβ-catenin and TNFRI protein expression in peripheral blood cells could represent molecular markers of sub-clinical disease in apparently healthy relatives of patients with early-onset UC.CONCLUSION:A synergistic effect of several variant alleles of the IL10 receptor genes,inherited in a Mende-lian manner,is involved in UC onset in this young child.

TLR4信号缺失对MPTP帕金森小鼠模型黑质Beta-catenin信号的表达影响

目的观察帕金森小鼠模型中TLR4通路对Beta-catenin信号的表达影响。方法 C57BL小鼠和TLR4敲除(TLR4knock out,TLR4 KO)小鼠各36只,分别注射生理盐水和1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)。采用RT-PCR、Westernblot检测4组之间的Beta-catenin的m RNA和蛋白表达变化,进一步采用免疫荧光的方法检测黑质区星形胶质细胞中Beta-catenin的共表达变化。结果 RT-PCR及Western blot结果显示,与生理盐水注射组小鼠相比,C57BL、TLR4KO小鼠在MPTP注射后,mRNA和蛋白表达明显升高(P<0.01);并且,与C57BL小鼠MPTP注射组相比,TLR4KO小鼠MPTP注射组Beta-catenin的mRNA和蛋白表达明显升高(P<0.01)。进一步的免疫荧光结果显示,与C57BL小鼠MPTP注射组相比,TLR4KO小鼠MPTP注射组星形胶质细胞(GFAP)中表达的beta-catenin明显升高。结论 TLR4通路在亚急性帕金森MPTP模型中,对黑质beta-catenin蛋白的表达起重要调控作用,Toll样信号与Beta-catenin信号这种互动关系可能在帕金森发病机制中起着重要的作用。

Wnt信号通路与肝再生的关系及其在肝脏疾病中的作用

Wnt信号通路在维持肝脏内稳态和肝脏再生过程中扮演重要角色,在成熟的健康肝脏中,Wnt信号通路大多是不活跃的,但在细胞更新或再生过程中,以及在某些病理条件、疾病、癌前状态和癌症中,Wnt信号通路被持续过度激活。持续的肝细胞损伤常常会导致慢性肝病,如肝纤维化、肝硬化及肝癌等。本文概述了Wnt信号通路的基本结构特点,详细分析了其在多种肝脏疾病病理进展所扮演的重要角色,希望为临床防治肝脏疾病提供新思路。

UVB诱导人皮肤成纤维细胞中beta-catenin基因的变化研究

目的:观察中波紫外线(UVB)诱导人皮肤成纤维细胞中β-catenin及其下游基因c-myc的变化,探讨其在紫外线诱导光老化和肿瘤发生中的作用。方法:使用组织块法分离培养原代成纤维细胞,使用第2～8代人皮肤成纤维细胞进行紫外线处理,倒置荧光显微镜观察其形态学改变,β-gal半乳糖苷酶细胞衰老试剂盒染色衰老细胞、western blot检测衰老相关蛋白P16的表达,western blot检测紫外线处理人皮肤成纤维细胞各时相点β-catenin、c-myc蛋白表达水平,RT-PCR检测紫外线处理人皮肤成纤维细胞各时像点β-catenin、c-mycmRNA水平的表达变化。结果:40mJ/cm2UVB单次照射后可以诱导人皮肤成纤维细胞衰老,β-gal衰老染色阳性率达到约90%,衰老相关基因P16蛋白表达明显升高,β-catenin、c-myc蛋白表达水平和mRNA水平照射后较未照射组均明显降低。结论:紫外线UVB处理人皮肤成纤维细胞可以诱导其发生衰老改变,衰老细胞中β-catenin、c-myc表达水平明显降低,这些结果与皮肤黑色素细胞瘤相关基因改变的研究相近,为以后皮肤恶性肿瘤的研究提供了线索。