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)

Tissue transglutaminase (TG2) affects cell-matrix interactions in cell spreading, migration and extracellular matrix (ECM) reorganisation. Using fibroblasts deficient in TG2 or overexpressing normal or crosslinking-deficient enzyme, we show that the extracellular crosslinking activity and intracellular G-protein function in signal transduction contribute differentially to regulation of cell-matrix interactions. TG2-deficient cells displayed normal attachment but delayed spreading on ECM substrata and defects in motility unrelated to crosslinking. Blocking antibodies to TG2 failed to induce similar defects in normal fibroblasts. TG2-deficient fibroblasts had defects in focal adhesion turnover and stress fibre formation, showed changes in focal adhesion kinase (FAK) phosphorylation and failed to activate protein kinase C alpha (PKCalpha). Phospholipase C (PLC) and PKCalpha inhibitors blocked spreading of normal fibroblasts whilst PKC activators induced spreading in TG2-deficient cells. In contrast, ECM remodelling was not only compromised by TG2 deficiency but also by overexpression of dominant negative enzyme and TG inhibitors. TG2 activity increased matrix tension and was required for membrane type 1-MMP (MT1-MMP)-dependent activation of MMP-2. Our results demonstrate that TG2 is involved in the control of dynamic adhesion formation in cell spreading and migration via regulation of phospholipase C activity. By virtue of its crosslinking activity, the enzyme plays a central role in regulating ECM remodelling.
 ...
PMID:Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses. 1519 98

Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix proteins, were investigated by means of immunohistochemistry on uterine biopsies of healthy mares and animals with endometrosis. It was illustrated that both proteins were present in fibrotic regions of affected endometria, and that they were in most cases colocalized. Periglandular MMP-2 expression was significantly associated with dilated and fibrotic uterine glands. Furthermore, MMP-2 and TG 2 were demonstrated in the stratum compactum of healthy and endometrotic endometria. Gelatin zymography proved that active and inactive pro-form of MMP-2 were present in all examined samples with significantly higher amounts of total and active MMP-2 in affected endometria. TG 2-activity, determined by an in situ assay, was found in cases of severe periglandular fibrosis. We suggest that both enzymes play a major role in changes that occur in ECM homeostasis in endometrial fibrotic regions.
 ...
PMID:Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis. 1613 93