Lussier C, Sodek J, Beaulieu J F
CIHR Group in Functional Development and Physiopathology of the Digestive Tract, Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec Canada.
J Cell Biochem. 2001;81(3):463-76.
SPARC is a glycoprotein of the extracellular matrix that exhibits a number of biological functions such as disruption of cell adhesion and modulation of matrix metalloprotease expression. These properties, in concert with the expression of the molecule during development, repair, and neoplastic progression, suggest that SPARC has an important role in remodeling in a variety of tissues. However, the role of SPARC in the intestine is unclear since the development expression and tissular origin of SPARC in this organ appears to be species-dependent. As a first step to investigate the function of SPARC in the tissues of the intestine, we have analyzed its expression at the protein and mRNA levels in the human fetal and adult small intestinal and colonic mucosa as well as in intestinal cell models. Our results show that SPARC expression is differentially regulated during development and along the length of the human intestine. In the colon, SPARC was predominantly found at the epithelial-mesenchymal interface at the fetal stage, below detection levels in the normal adult, but re-expressed in the stroma of colonic tumors. In the small intestine, low levels of SPARC expression were observed at an early stage of morphogenesis (between 9 and 11 weeks) but expression was not detected at subsequent developmental stages nor was it induced in the mucosa of Crohn's disease. While SPARC appeared to be produced mainly by mesenchymal and stromal cells in the intact intestine it was not detected in colon cancer cells. Taken together, these results indicate that SPARC is subject to an onco-fetal pattern of expression in the stroma of the colonic mucosa while its expression is much more restricted in the small intestine, suggesting a differential involvement of this molecule in the extracellular matrix remodeling occurring along the length of the developing and diseased human intestinal mucosa.
SPARC是一种细胞外基质糖蛋白，具有多种生物学功能，如破坏细胞黏附以及调节基质金属蛋白酶表达。这些特性，再加上该分子在发育、修复和肿瘤进展过程中的表达情况，表明SPARC在多种组织的重塑过程中发挥着重要作用。然而，SPARC在肠道中的作用尚不清楚，因为该器官中SPARC的发育表达和组织起源似乎具有物种依赖性。作为研究SPARC在肠道组织中功能的第一步，我们分析了其在人胎儿和成人小肠及结肠黏膜以及肠道细胞模型中的蛋白质和mRNA水平表达。我们的结果表明，SPARC的表达在发育过程中和人类肠道全长中受到不同的调节。在结肠中，SPARC主要在胎儿期的上皮-间充质界面处被发现，在正常成人中低于检测水平，但在结肠肿瘤的基质中重新表达。在小肠中，在形态发生早期（9至11周之间）观察到低水平的SPARC表达，但在随后的发育阶段未检测到表达，在克罗恩病黏膜中也未诱导表达。虽然在完整的肠道中SPARC似乎主要由间充质和基质细胞产生，但在结肠癌细胞中未检测到。综上所述，这些结果表明，SPARC在结肠黏膜基质中呈现癌胚性表达模式，而其在小肠中的表达则受到更多限制，这表明该分子在发育中和患病的人类肠道黏膜全长中发生的细胞外基质重塑中发挥着不同的作用。
