Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NH2-terminal amino acid sequences of thrombospondin and of a 30,000-Da heparin-binding peptide derived from thrombospondin by treatment with plasmin are identical. The heparin-binding peptide is homogeneous in size but slightly heterogeneous in charge with the predominant isoelectric points being 6.1 and 5.7. Electron microscopy of tungsten replicas of thrombospondin reveals a tripartite structure resembling a "bola" which is about 60 nm across when fully extended. Each part of the molecule terminates in a globular node or head which disappears upon limited plasmin digestion, suggesting that the heparin-binding peptide is located in the head region. In addition to the heparin-binding peptide, a 20,000-Da peptide also apparently associated with the head region is liberated during proteolysis. The electron micrographs indicate that the legs of the bola-like structure must be folded into an extended, flexible, tertiary structure. These legs, each of about 65,000 Da, appear to be attached near the ends opposite the heads, probably by disulfide bonds. Each leg possesses a tab or protein (approximately 20,000 Da) which juts out from this attachment point.
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PMID:Structure of thrombospondin. 623 Dec 89

Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal.
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PMID:Biomimetic delivery of keratinocyte growth factor upon cellular demand for accelerated wound healing in vitro and in vivo. 1631 71