Fibronectin Matrix Assembly after Spinal Cord Injury

After a spinal cord injury, scar tissue that contains glial and fibrotic components forms at the injury site. While the glial scar has received more attention, the fibrotic scar is made up of fibroblasts and a dense extracellular matrix (ECM). The fibrotic scar can inhibit axon growth, so understanding how it's formed may offer new insights into spinal cord injury pathology. Fibronectin, an extracellular matrix protein, is highly present in the fibrotic scar. After SCI, excess deposition of fibronectin comes from multiple sources, such as reactive astrocytes, macrophages, and fibroblasts. Fibronectin needs to polymerize into a fibrillar network to be a functional matrix, initiated by binding to cellular integrin receptors. However, whether or how this fibronectin matrix assembly occurs after SCI is not known. This study shows that fibronectin is assembled into a matrix to form the fibrotic scar, a process likely mediated by the fibronectin receptor integrin a5b1, which is primarily expressed by activated macrophages/microglia. The study also demonstrates the presence of fibrotic markers in a rat contusion model, highlighting the clinical relevance of the fibrotic scar.

• 1
  Fibroblasts are the major source of fibronectin in the fibrotic scar after spinal cord injury. Deletion of fibronectin in myeloid cells did not change fibronectin expression level, indicating that fibroblasts are likely the major source.
• 2
  Fibronectin is initially present in a soluble form after spinal cord injury, but assembles into a matrix at 7 days post-injury. This assembly is potentially mediated by the integrin a5b1 receptor, primarily expressed by activated macrophages/microglia in the fibrotic scar.
• 3
  A fibrotic scar is observed in a rat spinal cord injury model, which is considered more similar to human pathology, indicating the clinical relevance of the fibrotic scar.