PMC

Regulatory mechanisms controlling collagen homeostasis. This review will focus on the proposed function of SPARC in post-synthetic procollagen processing to influence collagen deposition in the heart.

Panel A: Procollagen processing into a mature collagen fibril in normal wild type (WT) mouse myocardium: 1. Procollagen secreted into the extracellular space. 2. SPARC binds to procollagen (or procollagen is secreted bound by SPARC). 3. SPARC decreases collagen association with cell surface receptors (or a subset of receptors). 4. C-terminal propeptide of procollagen cleaved by BMP-1 (enhanced by PCPE activity e.g. PCPE-1, PCPE-2, and Srfp2), 5. N-terminal propeptide cleaved by ADAMTS-2/14, 6. Collagen stabilized in mature fibrils by formation of cross-links.
Panel B: SPARC deletion alters the balance between processing to mature collagen fibrils and degradation; increased cell-associated collagen is degraded and/or taken up by cell-surface collagen receptors resulting in less procollagen effectively processed into mature fibrils and decreased levels of interstitial collagen assembled into insoluble fibers.
Panel C: SPARC over-expression further diminishes cell-associated collagen and promotes efficient procollagen processing and incorporation of collagen into fibrils thus enhancing deposition of collagen and formation of mature fibers.
SPARC: Secreted Protein Acidic and Rich in Cysteine, BMP: Bone Morphogenetic Protein, PCPE: Procollagen C-Proteinase Enhancer 1, other enhancers of activity include PCPE-2 and Srfp2. ADAMTS: A Disintegrin-like and Metalloproteinase Domain with Thrombospondin Type Motif, MT1-MMP: Membrane-Type Matrix Metalloproteinase.