Role of the Extracellular Matrix

Perris, R., Perissinotto, D. 2000. Role of the extracellular matrix during neural crest cell migration. Mech. Dev. 95, 3-21. 

Kleinman, H. K. Philp, D. Hoffman, M. P. Role of the extracellular matrix in morphogenesis. Curr. Opin. Biotechrwl. 2003,14,526-532. 

C. C. 1998. Ascorbic acid-induced choudrocyte termiual differeutiatiou The role of the extracellular matrix and 1,25-dihydroxyvitamin D. EurJ Cell Biol, 76, 110-8. 

Hyaluronic acid is a linear polysaccharide found in the highest concentrations in soft connective tissues where it fills an important structural role in the organization of the extracellular matrix (23,24). It has been used in ophthalmic preparations to enhance ocular absorption of timolol, a beta blocker used for the treatment of glaucoma (25), and in a viscoelastic tear formulation for conjunctivitis (26). The covalent binding of adriamycin and daunomycin to sodium hy-aluronate to produce water-soluble conjugates was recently reported (27). 

It has been demonstrated in other cell types that lutein can inhibit expression of MMPs and/ or activity (Philips et al., 2007). For example, in dermal fibroblasts lutein inhibits expression of MMP-1 and decreases levels of MMP-2 protein (Philips et al., 2007). In melanoma cells, lutein inhibits MMP-1 expression while stimulating TIMP-2 (Philips et al., 2007). Moreover it has been shown that lutein inhibits elastin expression in fibroblasts subjected to oxidative stress by exposure to ultraviolet light (Philips et al., 2007). These results clearly indicate that lutein can play an important role in remodeling of the extracellular matrix. 

A very innovative area of research has focused on the determinants of plaque stability. An important role seems to be played by enzymes involved in the degradation of the extracellular matrix. The rupture of unstable plaques induces platelet activation, too. Acute thrombus formation under these conditions seems fundamental to the onset of acute ischemic events. 

Targeting to SECs should be directed at specific receptors present on this ceU type. A wide range of proteins and other molecules can be taken up by SECs through receptor-mediated endocytosis. For example, SECs play an important role in the uptake of degradation prodncts of the extracellular matrix. For this purpose they have hyaluronan [6], (pro)coUagen, and fi-bronectin receptors [7]. The first two receptors are nniqnely located on SECs. Elevated levels of serum hyaluronan and fibronectin, that are often fonnd in Uver disease [8], are nsnally the result of dysfunction of the clearance capacity of SECs combined with an increased production by HSCs [9]. 

While the specific role of MTs is to neutralize ROS, MMPs contribute to tissue remodeling in both healthy and pathological muscle. MMPs process extracellular matrix proteins, cytokines and growth factors. Optimal remodeling of the extracellular matrix is contingent on tightly regulated MMP activity (Kjaer 2004). MMP... 

The addition of sugars is often required for a glycoprotein to function properly and reach its ultimate destination in the cell or organism. Glycoproteins are ffequendy present at the surface of cells where they function as membrane proteins or as part of the extracellular matrix. These cell surface glycoproteins play a critical role in cell-cell interactions and the mechanisms of infection by bacteria and viruses. 

Cuvelier, A. et al., Proteins of the inter-alpha trypsin inhibitor (ITI) family. A major role in the biology of the extracellular matrix, Rev. Mai. Respir., 17, 437, 2000. 

Cat B is an abundant and ubiquitously expressed cysteine peptidase of the papain family and makes up a major fraction of lysosomal enzymes that is capable of degrading components of the extracellular matrix in various diseases [30-32]. Cat B is also a prognostic marker for several types of cancer [33], and increased expression and secretion of cat B has been shown to be involved in the migration and invasion of various tumours [34—36], The precise role of cat B in solid tumours is not fully understood, but it has been proposed to participate, along with other cysteine cathepsins, in metastasis, angiogenesis, and tumour progression [37], Indeed, cat B inhibitors reduce both tumour cell motility and invasiveness in vitro [38], Recently, metal complexes based on rhenium, gold and palladium were shown to be effective inhibitors of cat B [39-44],... 

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