Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wound repair is characterized by the presence of a fibrin-rich matrix, but the effect of fibrin on re-epithelialization remains unclear. In this study, we determined the effects of different fibrin matrices on cultured human neonatal keratinocytes. Using purified fibrinogen and fibrin gels generated by the enzymatic action of thrombin, batroxobin (it leads to retention of fibrinopeptide B), or Agkistrodon contortrix thrombin-like enzyme (ACTE; it leads to retention of fibrinopeptide A), we determined the effect of each of these matrices on keratinocyte morphology, attachment, spreading, and replication as compared to tissue culture plastic. Morphologically, keratinocytes seeded on fibrin surfaces were more rounded and formed three-dimensional structures. Specific cell attachment, as measured at either 37 degrees C or 4 degrees C, was not altered on the different fibrin substrates (P > .05) but was increased on fibrinogen and factor XIII cross-linked fibrin (P < .01). However, keratinocytes seeded on fibrin, regardless of the presence or absence of fibrinopeptides A or B, showed a marked decrease (up to 71%) in cell numbers by days 5 (P = .0357) and 10 (P = .0114). Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes. However, either the addition of fibronectin or cross-linking of fibrin with factor XIII allowed full keratinocyte spreading to occur (P = .0002 and P = .0013, respectively). We conclude that fibrin inhibits keratinocyte spreading in the absence of other matrix or plasma proteins or cross-linking by factor XIII.
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PMID:Un-cross-linked fibrin substrates inhibit keratinocyte spreading and replication: correction with fibronectin and factor XIII cross-linking. 939 56

The transition of fibrinogen to fibrin and to their degradation products within the arterial wall has been reported to be accompanied by atherosclerotic progression. A major step in the pathogenesis of atherosclerosis is the vectorial migration of vascular smooth muscle cells (SMCs) from the arterial media through the internal elastic lamina into the intima and their subsequent proliferation in the intima. I have been studying the effects of fibrinogen, fibrin and their degradation products on the behaviour, particularly migration, of SMCs. Fibrinogen/fibrin stimulates the adhesion and migration of SMCs and their effects are mediated by both the RGD-containing region of the alpha chain of fibrinogen/fibrin and integrin alpha v beta 3 on the cell surface. SMCs migrate into fibrin gel even with no other chemotactic stimuli. SMCs displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of SMCs. Fibrin gels prepared with batroxobin, which cleaves only fibrinopeptide A, with ACTE, which cleaves only fibrinopeptide B, and with protamine sulfate, which cleaves nothing, but forms a fibrin-like gel, induce migration of SMCs in a manner similar to the gel prepared with thrombin, suggesting that the cleavage of fibrinopeptides is not involved in the migration of SMCs. Both anti-fibrinogen fragment D and E antibodies inhibit the migration of SMCs into fibrin gel, suggesting that both D and E regions of fibrin are involved in the migration of SMCs into fibrin gel. The migration of SMCs into fibrin gel also depends on the RGD-containing region and integrin alpha v beta 3. Both fibrinogen fragments D and E inhibit the migration of SMCs into fibrin gels, suggesting that these fragments may be involved in the regulation of SMC migration into fibrin gel as the result of fibrinolysis. Although subcultured SMCs usually show a synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. We employed an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. alpha v beta 3 integrin and the RGD-containing region are involved in the migration of SMCs into the fibrin gels. SMCs which migrated from the explants showed positive staining with monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from a contractile to synthetic state. These findings show that fibrin (ogen) itself induces adhesion and migration of SMCs without other chemotactic or chemokinetic substances, suggesting a crucial role for fibrin (ogen) in the development and progression of such vascular diseases as atherosclerosis, thrombosis and restenosis following balloon angioplasty.
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PMID:[Effects of fibrinogen, fibrin and their degradation products on the behaviour of vascular smooth muscle cells]. 1099 26