DIFFERENT SUSCEPTIBILITY OF SMALL AND LARGE HUMAN TENASCIN-C ISOFORMSTO DEGRADATION BY MATRIX METALLOPROTEINASES

Two major tenascin-C (TN-C) isoforms are generated by the alternative splicing of the pre-mRNA. The large isoform contains seven extra type three repeats that, by contrast, are omitted in the small TN-C isoform , The large TN-C isoform is mainly expressed at the onset of cellular processes that entail active cell migration, proliferation, or tissue remodeling such as occur in neoplasia, wound healing, and during devel opment. Thus, the large TN-C isoform seems to be a specific component of the provisional extracellular matrix. Here we have studied the degr adation of the large and small TN-C isoforms by matrix metalloproteina ses (MMPs) 2, 3, 7, and 9. Among these proteolytic enzymes only MMP-7 can degrade the small TN-C isoform removing the NH2-terminal knob. The large TN-C isoform shows the same MMP-7-sensitive site adjacent to th e NH2-terminal sequence, but is further degraded in the splicing area where three fibronectin-like type III repeats are completely digested. Moreover, the large TN-C isoform is degraded by MMP-2 and MMP-3 which completely digest a single type III repeat inside the splicing area. By contrast, the large TN-C isoform is resistant to MMP-9 digestion. T he results show that the presence of the spliced sequence introduces n ew protease-sensitive sites in the large TN-C isoform.