A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation.
Here we show that plasma kallikrein (PKal) mediates a plasminogen (Plg) cascade in adipocyte differentiation. Ecotin, an inhibitor of serine proteases, inhibits cell-shape change, adipocyte-specific gene expression, and lipid accumulation during adipogenesis in culture. Deficiency of Plg, but not of urokinase or tissue-type plasminogen activator, suppresses adipogenesis during differentiation of 3T3-L1 cells and mammary-gland involution. PKal, which is inhibited by ecotin, is required for adipose conversion, Plg activation and 3T3-L1 differentiation. Human plasma lacking PKal does not support differentiation of 3T3-L1 cells. PKal is therefore a physiological regulator that acts in the Plg cascade during adipogenesis. We propose that the Plg cascade fosters adipocyte differentiation by degradation of the fibronectin-rich preadipocyte stromal matrix.
Department of Anatomy, Box 0452, University of California, 513 Parnasssus Avenue, San Francisco, California 94143, USA.
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Selvarajan
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Lund
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Takeuchi
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CS
Craik
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Werb
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D001426:Bacterial Proteins / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003029:Coagulants / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism; D016895:Culture Media, Serum-Free; D029968:Escherichia coli Proteins; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000166:cytology; D051379:Mice; D033903:Periplasmic Proteins; D020842:Plasma Kallikrein / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D001391:Azo Compounds; D001426:Bacterial Proteins; D003029:Coagulants; D004396:Coloring Agents; D016895:Culture Media, Serum-Free; C039076:Eco protein, E coli; D029968:Escherichia coli Proteins; D005353:Fibronectins; D033903:Periplasmic Proteins; D015842:Serine Proteinase Inhibitors; D010958:Plasminogen; D020842:Plasma Kallikrein; D005341:Fibrinolysin; C011049:oil red O