Assessment of seminal plasma laminin in fertile and infertile men

Aim： To assess laminin levels in the seminal plasma of infertile and fertile men, and to analyze the correlation of laminin levels with sperm count, age, sperm motility and semen volume. Methods： One hundred and twenty-five recruited men were equally divided into five groups according to their sperm concentration and clinical examination： fertile normozoospermia, oligoasthenozoospermia, non-obstructive azoospermia （NOA）, obstructive azoospermia （OA） and congenital bilateral absent vas deferens （CBAVD）. The patients＇ medical history was investigated and patients underwent clinical examination, conventional semen analysis and estimation of seminal plasma laminin by radioimmunoassay. Results： Seminal plasma laminin levels of successive groups were： 2.82 ± 0.62, 2.49 ± 0.44, 1.77 ± 0.56, 1.72 ± 0.76, 1.35 ± 0.63 U/mL, respectively. The fertile normozoospermic group showed the highest concentration compared to all infertile groups with significant differences compared to azoospermic groups （P 〈 0.05）. Testicular contribution was estimated to be approximately one-third of the seminal laminin. Seminal plasma laminin demonstrated significant correlation with sperm concentration （r = 0.460, P 〈 0.001） and nonsignificant correlation with age （r = 0.021, P = 0.940）, sperm motility percentage （r = 0.142, P = 0.615） and semen volume （r = 0.035, P = 0.087）. Conelusion： Seminal plasma laminin is derived mostly from prostatic and testicular portions and minimally from the seminal vesicle and vas deferens. Estimating seminal laminin alone is not conclusive in diagnosing different cases of male infertility.     

Activated Notch1 maintains the phenotype of radial glial cells and promotes their adhesion to laminin by upregulating nidogen

Radial glia are neural stem cells that exist only transiently during central nervous system (CNS) development, where they serve as scaffolds for neuronal migration. Their instability makes them difficult to study, and therefore we have isolated stabilized radial glial clones from E14.5 cortical progenitors (e.g., L2.3) after expression of v-myc. Activated Notch1 intracellular region (actNotch1) promotes radial glia in the embryonic mouse forebrain (Gaiano et al., (2000), and when it was introduced into E14.5 cortical progenitors or radial glial clone L2.3, the cells exhibited enhanced radial morphology and increased expression of the radial glial marker BLBP. A representative clone of L2.3 cells expressing actNotch1 called NL2.3-4 migrated more extensively than L2.3 cells in culture and in white matter of the adult rat spinal cord. Microarray and RT-PCR comparisons of mRNAs expressed in these closely related clones showed extensive similarities, but differed significantly for certain mRNAs including several cell adhesion molecules. Cell adhesion assays demonstrated significantly enhanced adhesion to laminin of NL2.3-4 by comparison to L2.3 cells. The laminin binding protein nidogen was the most highly induced adhesion molecule in NL2.3-4, and immunological analyses indicated that radial glia synthesize and secrete nidogen. Adhesion of NL2.3-4 cells to laminin was inhibited by anti-nidogen antibodies and required the nidogen binding region in laminin, indicating that nidogen promotes cell adhesion to laminin. The combined results indicate that persistent expression of activated Notch1 maintains the phenotype of radial glial cells, inhibits their differentiation, and promotes their adhesion and migration on a laminin/nidogen complex.     

细胞外基质金属蛋白酶诱导因子和层黏连蛋白受体在人脑胶质瘤中的表达及意义

目的 探讨细胞外基质金属蛋白酶诱导因子(CD147)和层黏连蛋白受体(LN-R)在胶质瘤中的表达及意义.方法 采用RT-PCR对48例人脑胶质瘤组织的CD147和LN-R的mRNA表达情况进行半定量分析.结果 胶质瘤CD147和LN-R mRNA的阳性表达率分别为66.67%和58.33%,联合表达率为56.25%,两者之间存在正相关(r=0.815,P＜0.01).随着胶质瘤级别增高、侵袭能力增强,CD147和LN-R的mRNA表达水平也相应增高.结论 CD147和LN-R表达与胶质瘤恶性程度密切相关,其可作为判断胶质瘤病人临床预后和治疗有效的参考指标.     

当归对大鼠缺血性脑损伤再灌注后血管生成的影响

目的:观察大鼠缺血性脑损伤再灌注后,当归对血管内皮生长因子(vascularendotheliargrowthfactor,VEGF)层粘连蛋白(laminin)表达的影响。方法:65只雄性Wistar大鼠,体重160—180g,随机分成假手术组(A组),缺血组(B组)和当归组(C组)。制作右大脑中动脉血供阻断(MCAO)模型,缺血2h后,恢复灌注。通过免疫组织化学方法观察与血管生成密切相关的VEGF和层粘连蛋白在缺血损伤再灌注后3h,6h,12h,1d,3d,7d变化。结果:C组除再灌注后3h外各个相应时间点VEGF蛋白表达明显增加,与B组和A组相比较差异有显著意义(P<0.05);C组层粘连蛋白在缺血再灌后3d,7d时较A组和B组明显增多(P<0.05)。结论:当归促进缺血性脑损伤后血管生成,可能是当归治疗缺血性脑损伤的机制之一。     

血清抗层粘连蛋白—IgG（LN—IgG）与心肌疾病的关系

为探讨心肌疾病与自身免疫性损伤的关系,本文对９８例临床诊断各种心血管疾病患者的血清,用自建的抗层粘连蛋白－ＩｇＧ（ＬＮ－ＩｇＧ）检测法和国产抗心膦脂－ＩｇＧ（ＡＣＬ－ＩｇＧ）试剂进行了酶联免疫法的检测。结果为５３例心肌炎中１６例阳性,１２例心肌病中６例阳性,阳性率分别为３０．２％和５０％,而３３例心肌疾病中仅３例阳性,阳性率为９．１％,检测结果有显著性差异,而ＡＣＬ－ＩｇＧ检测结果无显著性差异。由此认为血清ＬＮ－ＩｇＧ阳性水平与心肌关系较为密切,在一定程度上反映了该类疾病主要以器官牧特异性的自身免疫性损伤为特征,有助于认识此类疾病的病因,发病机制和病程发展,在是否要取特异性免疫抑制疗法等方面具有一定价值。     

阵发性房颤患者血中纤维化指标的水平及意义

目的研究阵发性房颤患者血中纤维化指标的水平及意义。方法60例阵发性房颤患者及60例正常对照组分别测定血清Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)、透明质酸(HA)和层黏连蛋白(LN)并进行组间比较。结果阵发性房颤组血清中PCⅢ、CIV、HA及LN水平分别为(156.1±10.5)μg/L(、119.6±11.5)μg/L(、126.3±10.0)μg/L(、127.5±7.3)μg/L,明显高于正常对照组[(88.6±11.3)μg/L、(71.6±11.0)μg/L、(69.6±9.7)μg/L(、97.9±6.8)μg/L],均P<0.05。结论阵发性房颤患者血清中纤维化指标水平增高,提示阵发性房颤患者存在心房间质的纤维化。     

67 ku层黏连蛋白受体与肿瘤侵袭和转移

层黏连蛋白是细胞外基质重要的成分之一。67 ku层黏连蛋白受体(67 ku laminin receptor,67 LR)是层黏连蛋白的一个非整合素受体。它是一种多功能蛋白,既参与核糖体的组装、成熟过程,又参与细胞的信号转导,还可作为多种病毒的细胞膜受体。可以和层黏连蛋白相互作用,调节肿瘤的增殖、黏附、微血管形成,加速细胞外基质的降解,促进肿瘤的侵袭转移,其作用机制可能与MAPK信号通路有关。67 LR在多种肿瘤中高表达,还可以作为肿瘤免疫治疗的靶标。     

水蛭宣痹化纤汤对特发性肺纤维化大鼠TGF-β1、LN的影响

目的：探讨水蛭宣痹化纤汤对特发性肺纤维化大鼠转化生长因子-β1（TGF-β1）、层粘连蛋白（LN）的影响。方法：60只大鼠随机分为5组,除正常对照组,其他4组采用暴露气管注射博莱霉素法建立特发性肺纤维化大鼠模型,给药21天后,腹主动脉取血2mL离心得到血清,用酶联免疫吸附法（ELIsA）检测TGE-β1、LN的含量。结果：水蛭宣痹化纤汤能显著减少大鼠血清中TGF-β1、LN含量。结论：水蛭宣痹化纤汤通过调节TGF-β1、LN的含量达到抑制纤维化发展的作用,提示该药可用于人类特发性肺纤维化的防治。     

Revisiting laminin and extracellular matrix remodeling in metastatic squamous cell carcinoma: What have we learned after more than four decades of research?

Patients with squamous cell carcinoma (SCC) have significantly lower survival upon the development of distant metastases. The extracellular matrix (ECM) is a consistent yet dynamic influence on the metastatic capacity of SCCs. The ECM encompasses a milieu of structural proteins, signaling molecules, and enzymes. Just over 40 years ago, the fibrous ECM glycoprotein laminin was identified. Roughly four decades of research have revealed a pivotal role of laminins in metastasis. However, trends in ECM alterations in some cancers have been applied broadly to all metastatic diseases, despite evidence that these characteristics vary by tumor type. We will summarize how laminins influence the SCC metastatic process exclusively. Enhanced laminin protein deposition occurs at the invasive edge of SCC tumors, which correlates with elevated levels of laminin-binding β1 integrins on SCC cells, increased MMP-3 presence, worse prognosis, and lymphatic dissemination. Although these findings are significant, gaps in knowledge of the formation of a premetastatic niche, the processes of intra- and extravasation, and the contributions of the ECM to SCC metastatic cell dormancy persist. Bridging these gaps requires novel in vitro systems and animal models that reproduce tumor–stromal interactions and spontaneous metastasis seen in the clinic. These advances will allow accurate assessment of laminins to predict responders to transforming growth factor-β inhibitors and immunotherapy, as well as potential combinatorial therapies with the standard of care. Such clinical interventions may drastically improve quality of life and patient survival by explicitly targeting SCC metastasis.     

Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function

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