A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation

Here we show that plasma kallikrein (PKal) mediates a plasminogen (Plg) cas cade 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 pig, but not of urokinase or tissue-type plasminogen activator, suppresses adipogenesis du ring differentiation of 3T3-L1 cells and mammary-gland involution. PKal, wh ich is inhibited by ecotin, is required for adipose conversion, pig activat ion and 3T3-L1 differentiation. Human plasma lacking PKal does not support differentiation of 3T3-L1 cells. PKal is therefore a physiological regulato r that acts in the pig cascade during adipogenesis. We propose that the pig cascade fosters adipocyte differentiation by degradation of the fibronecti n-rich preadipocyte stromal matrix.