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A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation

Nature Cell Biology volume 3, pages 267–275 (2001)Cite this article

Abstract

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.

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Figure 1: Inhibition of serine proteases during differentiation of 3T3-L1 cells reduces adipose conversion.
Figure 2: The Plg system is regulated and required during 3T3-L1 cell differentiation.
Figure 3: Adipogenesis is reduced in female mice treated with ecotin during mammary-gland involution.
Figure 4: Adipocyte differentiation is impaired during involution in Plg-deficient, but not uPA-deficient, mice.
Figure 5: PKal is present during adipogenesis and is required for differentiation of 3T3-L1 cells.
Figure 6: Plg and PKal promote adipose conversion in the absence of FBS.
Figure 7: PKal-mediated Plg activation promotes fibronectin degradation during adipocyte differentiation.

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Acknowledgements

This work was supported by grants from the National Cancer Institute (to C.S.C. and Z.W.).

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Authors and Affiliations

  1. Department of Anatomy, Box 0452, University of California, 513 Parnasssus Avenue, San Francisco, 94143, California, USA

    Sushma Selvarajan & Zena Werb

  2. Department of Pharmaceutical Chemistry, Box 0446, University of California, 513 Parnasssus Avenue, San Francisco, 94143, California, USA

    Sushma Selvarajan, Leif R. Lund, Toshihiko Takeuchi & Charles S. Craik

  3. Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, Copenhagen, DK-2100, Denmark

    Leif R. Lund

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Correspondence to Zena Werb.

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Selvarajan, S., Lund, L., Takeuchi, T. et al. A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation. Nat Cell Biol 3, 267–275 (2001). https://doi.org/10.1038/35060059

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