Abstract
The matricellular protein SPARC (also known as osteonectin and BM‐40) is expressed abundantly in lens epithelium. That SPARC‐null mice exhibit early cataractogenesis, indicates a role for SPARC in the maintenance of lens transparency. Comparison of cultured wild‐type and SPARC‐null lens epithelial cells revealed significant changes in adhesion to different substrates. SPARC‐null lens cells displayed enhanced attachment and spreading, focal adhesion formation, and resistance to trypsin detachment in comparison to wild‐type cells. In the absence of SPARC, there was increased deposition of the ECM protein laminin‐1 (LN‐1). Proteins associated with focal adhesions were increased in SPARC‐null versus wild‐type lens cells: levels of α6‐integrin heterodimers, talin, and paxillin phosphorylated on tyrosine were enhanced significantly, as was the association of β1‐integrin with talin and paxillin. Restoration of the wild‐type phenotype in SPARC‐null cultures was accomplished through genetic rescue by stable transfection of SPARC cDNA. Our findings indicate that SPARC is counter‐adhesive for murine lens epithelial cells and demonstrate that multiple factors contribute to this activity. We also identify SPARC as a modulator of LN‐1 secretion and deposition by these cells, an activity important in epithelial cell‐ECM interactions in the ocular lens. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.