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Tissue cooperation in a proteolytic cascade activating human interstitial collagenase.
C S HE1, S M Wilhelm, A P Pentland
1Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110.
Summary
Skin cell interactions activate interstitial procollagenase through a cascade involving urokinase and plasmin. This process enhances collagenase activity, crucial for tissue remodeling.
Area of Science:
- Biochemistry
- Cell Biology
- Dermatology
Background:
- Cultured human skin fibroblasts secrete interstitial collagenase and stromelysin as proenzymes.
- Interstitial collagenase in serum-free skin organ culture medium is activated.
- Cocultivation of dermal fibroblasts and epidermal keratinocytes induces procollagenase and prostromelysin activation.
Purpose of the Study:
- To elucidate the proteolytic cascade leading to interstitial procollagenase activation in skin organ cultures.
- To investigate the roles of keratinocytes, fibroblasts, plasminogen, and urokinase in this activation process.
Main Methods:
- Utilized cultured keratinocytes and fibroblasts.
- Employed serum-free skin organ culture and cocultivation techniques.
- Investigated the effects of plasminogen and urokinase on procollagenase and prostromelysin activation.
Main Results:
- Keratinocytes secrete urokinase, activating plasminogen to plasmin.
- Plasmin activates both interstitial procollagenase and prostromelysin.
- Activated stromelysin further processes plasmin-activated collagenase, increasing its specific activity 5- to 8-fold.
- Stromelysin alone does not efficiently activate human fibroblast interstitial procollagenase.
Conclusions:
- A urokinase-dependent proteolytic cascade involving plasmin activates interstitial procollagenase and prostromelysin in skin organ cultures.
- Stromelysin plays a key role in amplifying collagenase activity through post-translational modification.
- This cascade is critical for regulating collagenase activity in skin tissue.