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Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis.

Nature Medicine volume 7, pages 324–330 (2001)Cite this article

Abstract

Fibronectin performs essential roles in embryonic development and is prominently expressed during tissue repair. Two forms of fibronectin have been identified: plasma fibronectin (pFn), which is expressed by hepatocytes and secreted in soluble form into plasma; and cellular fibronectin (cFn), an insoluble form expressed locally by fibroblasts and other cell types and deposited and assembled into the extracellular matrix. To investigate the role of pFn in vivo, we generated pFn-deficient adult mice using Cre-loxP conditional gene-knockout technology. Here we show that pFn-deficient mice show increased neuronal apoptosis and larger infarction areas following transient focal cerebral ischemia. However, pFn is dispensable for skin-wound healing and hemostasis.

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Figure 1: Generations of pFn-null mice.
Figure 2: Evaluation of hemostasis.
Figure 3: Histology and deposition of fibronectins during skin-wound healing.
Figure 4: Evaluation of infarct size.
Figure 5: Evaluation of cell death.
Figure 6: Integrin immunostaining in the normal adult striatum of the brain.

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Acknowledgements

We thank W. Müller for providing Mx-Cre mice; J.F. Talts and K. Sekiguchi for mouse fibronectin cDNA; D.F. Mosher for human plasma fibronectin; E. Georges-Labouesse for antibody; and R. Timpl for discussions and critical reading of the manuscript. The work was supported by The Scandinavia-Japan Sasakawa Foundation (to T.S.), National Institute of Health grant CA47056 (to H.P.E), the Swedish Medical Research Council (K98-12X-12531-01A, to R.F.) and the SSF-Inflammation Program (to R.F.).

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Authors and Affiliations

  1. Department of Experimental Pathology, Lund University, Lund, Sweden

    Takao Sakai, Kamin J. Johnson, Keiko Sakai & Reinhard Fässler

  2. Wallenberg Neuroscience Center, Lund University, Lund, Sweden

    Michihiro Murozono, Tadeuz Wieloch & Tobias Cronberg

  3. Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA

    Kamin J. Johnson

  4. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA

    Kamin J. Johnson & Harold P. Erickson

  5. Department of Anesthesiology, Tokyo Medical University, Tokyo, Japan

    Michihiro Murozono & Atsushi Isshiki

  6. Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Tennesee, USA

    Marc A. Magnuson

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Correspondence to Reinhard Fässler.

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Sakai, T., Johnson, K., Murozono, M. et al. Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis.. Nat Med 7, 324–330 (2001). https://doi.org/10.1038/85471

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