“A Matricellular Protein for All Seasons: SPARC and Hevin in Development and Pathology ”
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Abstract: Matricellular proteins were originally defined as extracellular macromolecules that modulate cell-extracellular matrix (ECM) interactions; as such, they do not act as classical structural proteins, e.g., collagen and laminin.  Matricellular proteins accomplish their function through several different mechanisms that include interaction with growth factors, cytokines, and/or proteases, binding to structural macromolecules of the ECM, and modulation of ECM assembly.  Some readouts of matricellular protein function include modulation of:  1) cell shape and adhesion, 2) survival, 3) proliferation, and 4) differentiation. 
SPARC and hevin are homologous proteins that were among the first characterized members of the matricellular group.  Both affect ECM assembly and cell adhesion.  The SPARC-null mouse develops a plethora of characteristics that include cataracts, osteopenia, degeneration of the intervertebral disc, an attenuated dermis, and enhanced accumulation of adipose tissue.  Hevin-null mice also have alterations in their dermis but do not exhibit the diversity of characteristics seen in the SPARC-null mouse.  Both animals show enhanced wound closure relative to wild-type counterparts and appear to influence collagen fibril formation.  It is of interest that the foreign body response in mice can be substantially influenced by either protein:  hevin-null mice show an enhanced recruitment of macrophages/foreign body giant cells, whereas SPARC-null mice show a profound decrease in the synthesis of the capsule surrounding the implant.  An apparent compensatory function afforded by both proteins is an inhibition of angiogenesis. 
We have recently shown that SPARC activates integrin-linked kinase which actuates the assembly of extracellular fibronectin.  Moreover, a scavenger receptor termed stabilin-1 has been identified as a mechanism by which excess SPARC can be cleared from the extracellular milieu, thereby titrating its effects on cells.