Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical studies of prostate carcinoma reveal that most primary carcinomas, including high-grade tumors, are surrounded by a basal lamina composed of laminin, type IV collagen, and entactin. In addition to the expected laminin subchains A, B1, B2, subchains M and S are also found. Tenascin, found around normal glands, is seen in 60% of carcinomas. The basal cells of the normal gland express several integrin alpha units including alpha 2,3,4,5,6, and v. Both beta 1 and beta 4 subunits are observed. These integrin units are polarized at the base of the cells where they codistribute with the surrounding extracellular matrix. The integrin alpha 6 beta 4 is associated with hemidesmosomal-like structures, as detected by transmission electron microscopy (TEM). In carcinoma, the beta 4 is not observed and the alpha 6 and beta 1 subunits are variably expressed. The integrin expression in carcinoma is diffuse in the cytoplasmic membrane and not restricted to the basal aspects of the cell. In addition, type VII collagen and the BP 180 protein which are associated with hemidesmosomes are lost, although the BP 230, plectin, and HD1 proteins are variably expressed. Using immunohistochemistry and northern analysis we observed three metalloproteinases in prostate carcinoma--matrilysin, gelatinase A, and gelatinase B. Western blotting and zymogram analysis reveal that of these three, only matrilysin appears to be present in its active form. Recent in situ hybridization studies reveal focal expression of the matrilysin mRNA in 25/33 primary carcinomas. Matrilysin also appears to be highly expressed in prostatic ducts and atrophic glands. Expression of the three metalloproteinases is also seen in prostatic intraepithelial neoplasia lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma. 782 96

Disintegration of the basement membrane (BM) of the equine hoof lamellae and failure of the BM to remain attached to the basal cells of the secondary epidermal lamellae (SEL) is one of the earliest pathological events to occur in acute laminitis. Changes in the lamellar basement membrane were investigated by immunolabelling the key structural components of the BM, type IV collagen, type VII collagen and laminin in the lamellar BM of horses 48 h after the induction of laminitis. Lamellar tissues were harvested from 2 normal horses and 2 horses with acute laminitis. Immunostaining with antibody raised against human epitopes for type IV collagen, type VII collagen and laminin successfully stained the basement membranes of horse hoof lamellar tissues. Vascular tissue did not immunostain with type VII collagen antibody. Normal BM stained as a fine dark brown line and the lamellar BM was adhered to the basal cells of the SELs with no evidence of lamellar separation. At least 2 changes to the lamellar BM occurred in acute laminitis: loss of attachment of lamellar epidermal basal cells to their underlying BM and disintegration of the lamellar BM. In some sections from feet affected by acute laminitis, there was widespread separation of the SELs from their BM without loss of BM immunostaining and in others there was extensive loss of BM immunostaining. In lesions characterised by lamellar separation, the epidermal basal cells at the tips of the primary epidermal lamellae appeared to have slipped away from their BM and were an amorphous clump of epidermal cells devoid of immunostained BM. The BM from which they had separated remained in its original position in the dermis and was clearly outlined by all 3 antibodies. In other areas, however, virtually all the BM immunoreactivity at the PEL tips was absent. Only the occasional distorted SEL tip and fragments of BM retained sufficient immunostaining to allow anatomical identification. Numerous polymorphonuclear leucocytes (PMNs) invariably surrounded the tips of lamellae showing large scale loss of immunoreactivity and many PMNs had penetrated the lamellar BM and were within the epidermal compartments. PMNs were less frequent in the midlamellar region. Immunostaining of the BM of many SELs was absent in the midlamellar region. In some lamellae loss of BM immunostaining had occurred only at the bases of the SELs and fragments of immunostained BM were present in the zones of lysed BM suggesting that BM lysis was incomplete at the time of tissue fixation. In other lamellae, lysis of the BM was complete; there was no immunostained BM between SELs and the bulk of the epidermal cells of each PEL were an amorphous column of cells on either side of the central keratinised axis of the PEL. The lamellar BM which remained appeared as immunostained strands of unattached BM along the edges of the PDLs. Activation of BM degrading metalloproteinases (MMPs) occurs in acute laminitis and it seems likely that uncontrolled MMP activity is responsible for the loss and disorganisation of lamellar BM demonstrated in this study.
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PMID:Equine laminitis basement membrane pathology: loss of type IV collagen, type VII collagen and laminin immunostaining. 993 5