A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation

Nat Cell Biol. 2001 Mar;3(3):267-75. doi: 10.1038/35060059.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / physiology
  • Animals
  • Azo Compounds / metabolism
  • Bacterial Proteins / pharmacology
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Coagulants / metabolism*
  • Coloring Agents / metabolism
  • Culture Media, Serum-Free
  • Escherichia coli Proteins*
  • Female
  • Fibrinolysin / metabolism
  • Fibronectins / metabolism
  • Humans
  • Immunohistochemistry
  • Mammary Glands, Animal / anatomy & histology
  • Mammary Glands, Animal / cytology
  • Mice
  • Periplasmic Proteins*
  • Plasma Kallikrein / metabolism*
  • Plasminogen / metabolism*
  • Serine Proteinase Inhibitors / pharmacology


  • Azo Compounds
  • Bacterial Proteins
  • Coagulants
  • Coloring Agents
  • Culture Media, Serum-Free
  • Eco protein, E coli
  • Escherichia coli Proteins
  • Fibronectins
  • Periplasmic Proteins
  • Serine Proteinase Inhibitors
  • Plasminogen
  • Plasma Kallikrein
  • Fibrinolysin
  • oil red O