Greiling Teri M S, Stone Brad, Clark John I
University of Washington, Department of Biological Structure, Seattle, WA 98195-7420, USA.
Exp Eye Res. 2009 Sep;89(3):416-25. doi: 10.1016/j.exer.2009.04.008. Epub 2009 May 3.
SPARC is a matricellular glycoprotein involved in regulation of extracellular matrix, growth factors, adhesion, and migration. SPARC-null mice have altered basement membranes and develop posterior sub-capsular cataracts with cell swelling and equatorial vacuoles. Exchange of fluid, nutrients, and waste products in the avascular lens is driven by a unique circulating ion current. In the absence of SPARC, increased circulation of fluid, ions, and small molecules led to increased fluorescein distribution in vivo, loss of resting membrane polarization, and altered distribution of small molecules. Microarray analysis of SPARC-null lenses showed changes in gene expression of ion channels and receptors, matrix and adhesion genes, cytoskeleton, immune response genes, and cell signaling molecules. Our results confirm the hypothesis that the regulation of SPARC on cell-capsular matrix interactions can increase the circulation of fluid and ions in the lens, and the phenotype in the SPARC-null mouse lens is the result of multiple intersecting functional pathways.
SPARC是一种基质细胞糖蛋白，参与细胞外基质、生长因子、黏附及迁移的调控。SPARC基因敲除小鼠的基底膜发生改变，并出现后囊下白内障，伴有细胞肿胀和赤道部空泡。无血管的晶状体中液体、营养物质及代谢废物的交换由独特的循环离子电流驱动。在缺乏SPARC的情况下，液体、离子及小分子的循环增加，导致体内荧光素分布增加、静息膜电位丧失以及小分子分布改变。对SPARC基因敲除晶状体的微阵列分析显示，离子通道和受体、基质和黏附基因、细胞骨架、免疫反应基因及细胞信号分子的基因表达发生了变化。我们的结果证实了以下假说：SPARC对细胞-囊膜基质相互作用的调控可增加晶状体中液体和离子的循环，且SPARC基因敲除小鼠晶状体的表型是多种相互交叉的功能途径的结果。
