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Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
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Plasminogen-Dependent Matriptase Activation Accelerates Plasmin Generation by Differentiating Primary Human
Ya-Wen Chen1, Shi Yin1, Ying-Jung J Lai1
1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
The Journal of Investigative Dermatology
|February 14, 2016
Summary
Plasminogen initiates matriptase activation in differentiating keratinocytes. This activates a feed-forward loop, enhancing pericellular proteolysis for robust cell function.
Area of Science:
- Cell Biology
- Biochemistry
- Dermatology
Background:
- Pericellular plasmin generation is crucial in pathophysiology.
- Matriptase (a serine protease) and urokinase plasminogen activator (uPA) are key players.
- Previously, the matriptase-plasminogen link was considered unidirectional.
Purpose of the Study:
- To investigate the role of plasminogen in matriptase activation during keratinocyte differentiation.
- To elucidate the signaling pathways involved in this process.
- To identify a potential feed-forward mechanism in pericellular proteolysis.
Main Methods:
- Primary human keratinocyte cultures.
- Calcium-induced differentiation.
- Serum treatment and signaling pathway analysis (intracellular calcium, PKC, PI3K).
- Zymogen activation assays.
- Cell surface protein analysis.
Main Results:
- Serum rapidly activates matriptase zymogen in differentiating keratinocytes.
- Plasminogen, at sub-pM concentrations, is the serum factor inducing matriptase activation.
- This activation is dependent on intracellular calcium, protein kinase C, and phosphatidylinositol 3-kinases.
- Active matriptase is shed and re-associates with the cell surface to accelerate plasmin generation.
- A potent feed-forward mechanism is revealed.
Conclusions:
- Plasminogen directly induces matriptase zymogen activation in differentiating keratinocytes.
- This initiates a robust feed-forward loop for pericellular proteolysis.
- The findings uncover a novel mechanism regulating cell surface proteolysis in human skin cells.
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