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

Josephine M. J. Stoffels, Chao Zhao, Wia Baron*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4243-4253
Number of pages11
JournalCellular and molecular life sciences
Volume70
Issue number22
DOIs
Publication statusPublished - Nov-2013

Keywords

  • Fibronectin
  • Wound healing
  • Osteoarthritis
  • Multiple sclerosis
  • Tissue regeneration
  • MEDIATED CARTILAGE CHONDROLYSIS
  • OLIGODENDROCYTE PRECURSOR CELLS
  • HUMAN ARTICULAR CHONDROCYTES
  • MULTIPLE-SCLEROSIS LESIONS
  • EXTRA DOMAIN-A
  • HUMAN OSTEOARTHRITIC CARTILAGE
  • CENTRAL-NERVOUS-SYSTEM
  • EXTRACELLULAR-MATRIX
  • PLASMA FIBRONECTIN
  • IN-VIVO

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