Molecular Scissors: From Biomaterials Implant to Tissue Remodeling - Biologically Responsive Biomaterials for Tissue Engineering - page 30

Fig. 2.9 MMPs involvement in healing steps. ( a ) Cell migration is facilitated by MMPs by degra-
dation of the adhesive and ECM proteins; ( b ) Re-epithelization—adhesion proteins are cleaved by
MMPs and cells involved in healing are promoted; ( c ) Leukocyte influx—chemokines and proteo-
glycans are cleaved by MMPs; ( d ) Inflammation step; MMPs are processing multiple chemokines
and stromal cells in wounds. In wound repair processes we may observe the
involvement of MMP-1, 2, 3, 7, 9, 10, or 28. Many of these MMPs may regulate
chemokine activity by direct proteolysis or by generating chemokine gradients.
Chemokines are divided in subfamilies based on N-terminal cysteinic residues
and play specific roles in attracting the leukocyte flow toward inflammation site.
CC chemokines are characterized by two neighbor cysteinic residues toward
N-terminus and are responsible for monocyte chemotaxis. CXC chemokines
show another amino acid between cysteine residues and are responsible for neu-
trophil attraction toward inflammation site. Chemokine effects are mediated by
binding to 7-domain-transmembrane G protein-coupled receptors (7-TM-GPCRs).
MMP-controlled chemokine cleavage induces a reduction of chemokine activity.