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Fibronectin in tissue regeneration: timely disassembly of the scaffold is necessary to complete the build

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Abstract

Tissue injury initiates extracellular matrix molecule expression, including fibronectin production by local cells and fibronectin leakage from plasma. To benefit tissue regeneration, fibronectin promotes opsonization of tissue debris, migration, proliferation, and contraction of cells involved in the healing process, as well as angiogenesis. When regeneration proceeds, the fibronectin matrix is fully degraded. However, in a diseased environment, fibronectin clearance is often disturbed, allowing structural variants to persist and contribute to disease progression and failure of regeneration. Here, we discuss first how fibronectin helps tissue regeneration, with a focus on normal cutaneous wound healing as an example of complete tissue recovery. Then, we continue to argue that, although the fibronectin matrix generated following cartilage and central nervous system white matter (myelin) injury initially benefits regeneration, fibronectin clearance is incomplete in chronic wounds (skin), osteoarthritis (cartilage), and multiple sclerosis (myelin). Fibronectin fragments or aggregates persist, which impair tissue regeneration. The similarities in fibronectin-mediated mechanisms of frustrated regeneration indicate that complete fibronectin clearance is a prerequisite for recovery in any tissue. Also, they provide common targets for developing therapeutic strategies in regenerative medicine.

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Acknowledgments

Work in the Baron Laboratory is supported by grants from the Netherlands Foundation for the Support of MS Research (Stichting MS Research), and the Netherlands Organization of Scientific Research NWO (VIDI and Aspasia).

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Authors and Affiliations

  1. Department of Cell Biology, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Josephine M. J. Stoffels & Wia Baron

  2. Wellcome Trust—Medical Research Council Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK

    Chao Zhao

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  1. Josephine M. J. Stoffels
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Correspondence to Wia Baron.

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Stoffels, J.M.J., Zhao, C. & Baron, W. Fibronectin in tissue regeneration: timely disassembly of the scaffold is necessary to complete the build. Cell. Mol. Life Sci. 70, 4243–4253 (2013). https://doi.org/10.1007/s00018-013-1350-0

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