An important element of tissue or organ morphogenesis is the selective effects of secreted proteins and other macromolecules on cellular behavior and differentiation. This chapter focuses on a prototypic member of one of these classes, the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and its role in cell and tissue biology. SPARC affects the manner in which cells interact with the extracellular matrix (ECM), including the growth factors with which the matrix is associated. Hence, SPARC exerts both counter-adhesive and antiproliferative effects on cells in vitro. , and presumably in vivo. Although structurally dissimilar, these proteins regulate interactions between cells and their ECM and feature prominently in morphogenesis, development, injury, and repair. SPARC has been shown to inhibit the cell cycle, disrupt cell adhesion, inactivate cellular responses to certain growth factors, regulate ECM and matrix metalloproteinase production, bind to specific collagens, and promote a rounded cell shape through dissolution of focal adhesions and reorganization of the actin cytoskeleton. SPARC-null mice are viable but exhibit phenotypic abnormalities associated with the eye, connective and adipose tissues, bone, and wound healing. Cells cultured from SPARC-null versus wild-type tissues show significantly accelerated cell cycles, diminished production of collagen and transforming growth factor β-1, enhanced adhesion, and/or altered levels of cadherins and matricellular proteins. Thus, the expression of SPARC in remodeling tissues, as a consequence of normal development or response to injury, coupled with its multiple effects on cells of the vessel wall, is consistent with the proposal that SPARC subserves a fundamental role in vascular morphogenesis and cellular differentiation.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)