Studies on extracellular matrix tenascin family

Tenascins是一个大的多聚体细胞外基质蛋白家族。该家族至少由5个脊椎动物相关蛋白组成：原始Tenascin(TnC，TNC)、TnR(TnR)、TnX(TnX)、新近发现的TnY(Tny)和TnW(TnW)。特别是，我们参与了TnX的发现，并首次在蛋白质水平上鉴定了TnX。在本研究中，我们试图揭示Tenascin家族成员之间的相互关系。特别是，我们披露了三个新的发现如下。首先，我们检测了TNX和TNC的表达模式，以揭示它们的表达是否与恶性程度成比例地变化。Tnx在低级别星形细胞瘤中的表达上调程度高于高级别星形细胞瘤。相反，在高级别星形细胞瘤中，TNC在细胞间隙和肿瘤血管中的表达强于低级别星形细胞瘤。在表达bo…的组织中其次，糖皮质激素可下调成纤维细胞中TNX基因的表达水平和蛋白质合成。与体内研究一样，将癌细胞移植到裸鼠体内。与成人皮肤中普遍存在的TNX相反，在肿瘤发生过程中，TNX蛋白的表达不仅在肿瘤细胞中显著下调，而且在肿瘤间质中也显著下调。这些发现提供的证据表明，TnX的表达可以受到基质-上皮相互作用的影响。我们已经确定糖皮质激素是TNX的生理抑制物，并提示糖皮质激素可能在体内部分参与下调成纤维细胞中TNX的表达。第三，我们测定了包括小鼠TnX基因座在内的67,977个碱基的序列。推测的氨基酸序列(4,114个残基)表明，小鼠TnX具有特征的一级结构，从4个Hed重复开始，接着是18.5个EGF重复和31个纤维连接蛋白III型(FNIII)结构域，最后是一个与纤维蛋白原同源的结构域。还鉴定了通过交替剪接8个连续的FNIII重复序列(M15-M22)以及近端的FNIII重复序列(M3)而产生的几个cDNA克隆。较少

Tenascins are a family of large multimeric extracellular matrix proteins. The family is comprised of at least five members of related proteins in vertebrated : the original tenascin (tenascin-C,TNC), tenascin-R (TNR), tenascin-X (TNX), recent discoverd tenascin-Y (TNY), and tenascin-W (TNW). Especially, we were involved in the discovery of TNX and was the first toidentify TNX on the protein level. In this study, we attempted to reveal the interrelationship among the tenascin family members. In particular, we have disclosed three new findings as follows. First, we examined the expression patterns of TNX and TNC to reveal whether their expression is changed in proportion to the grade of malignancy. Expression of TNX was up-regulated to a higher degree in low-grade astrocytomas than in high-tfade astrocytomas. In contrast, TNC was more strongly expressed in the intercellular spaces and in tumor vessels in high-grade astrocytomas than in low-grade astrocytomas. In the tissues expressing bo … More th TNs, the distribution of TNX was often reciprocal to that of TNC.Second, glucocorticoids were found to downregulate TNX mRNA levels and protein synthesis in fibroblasts. As in vivo study, carcinoma cells were transplanted into nude mice. In contrast to the ubiqutious presence of TNX in adult skin, expression of TNX protein during tumorigenesis was found to be down-regulated considerably not only in tumor cells themsclves but also in tumor stroma. These findings provide evidence that the expression of TNX can be influenced by stromal-epithelial interactions. We have identified glucocorticoids as physiological inhibitors of TNX and suggest that glucocorticoids may in part partcipate in the downregulation of TNX in fibroblast in vivo. Third, we determined a total of 67,977-bp sepuence including the mouse TNX loci. The deduced amino acid sequence (4,114 residues) reveals that mouse TNX has the characteristic primary structure, which begins with 4 hepted repeats, follows with 18.5 EGF repeats and 31 fibronectin type III-like (FNIII) domains, and concludes with a domain homologous to fibrinogen. Several cDNA clones that have been generated by alternative splicing of eight consecutive FNIII repeats (M15-M22), as well as a proximal FNIII repeat (M3), were also identified. Less