DIFFERENTIAL DISTRIBUTION OF 5 MEMBERS OF THE MATRIX METALLOPROTEINASE FAMILY AND ONE INHIBITOR (TIMP-1) IN HUMAN LIVER AND SKIN

Matrix metalloproteinases represent a family of zinc-dependent proteol ytic enzymes thought to be involved in normal and disease-related tiss ue remodeling processes. Increasing information about these enzymes is becoming available concerning their primary sequences, regulation at the mRNA level, activation of proenzymes, and modulation of enzyme act ivity by tissue inhibitors. In contrast, their morphological distribut ion and biological functions in normal tissues are poorly understood. In the present report, the comparative distribution of five members (g elatinase-A, gelatinase-B, matrilysin, stromelysin-l, and stromelysin- 3) of the matrix metalloproteinase family and of one inhibitor (TIMP-1 ) has been morphologically analyzed in human liver and skin with the a id of new monospecific antibodies. Because of their common designation as matrix proteinases, these enzymes might have been expected to be d istributed throughout these tissues, or at least in the connective tis sue. However, each member of the family produces a highly specific pat tern, staining structures such as arteriolar smooth muscle cells, myoe pithelial cells in secretory portions or the luminal lining in excreto ry ducts of dermal sweat glands, liver bile canaliculi, or structures surrounding peripheral nerve axons. No reactivity is detected in rat t issues.