Fibronectin Matrix Assembly after Spinal Cord Injury

Abstract

After spinal cord injury (SCI), a fibrotic scar forms at the injury site that is best characterized by the accumulation of perivascular fibroblasts and deposition of the extracellular matrix protein fibronectin. While fibronectin is a growth-permissive substrate for axons, the fibrotic scar is inhibitory to axon regeneration. The mechanism behind how fibronectin contributes to the inhibitory environment and how the fibronectin matrix is assembled in the fibrotic scar is unknown. By deleting fibronectin in myeloid cells, we demonstrate that fibroblasts are most likely the major source of fibronectin in the fibrotic scar. In addition, we demonstrate that fibronectin is initially present in a soluble form and is assembled into a matrix at 7 d post-SCI. Assembly of the fibronectin matrix may be mediated by the canonical fibronectin receptor, integrin α5β1, which is primarily expressed by activated macrophages/microglia in the fibrotic scar. Despite the pronounced cavitation after rat SCI, fibrotic scar also is observed in a rat SCI model, which is considered to be more similar to human pathology. Taken together, our study provides insight into the mechanism of fibrotic scar formation after spinal cord injury.

Tocotrienol alleviates inflammation and oxidative stress in a rat model of spinal cord injury via suppression of transforming growth factor-β

“…Fibronectin is a multifunctional glycoprotein found in the extracellular matrix and plasma (35). Widely existing in animal tissues and tissue fluid, fibronectin is a V-shaped macromolecular glycoprotein with a molecular weight of ~450 kDa and a variety of biological activities (36). Numerous international studies have shown that the fibronectin molecule is highly conserved in the evolution process, and various animal body fluids share similar structure, properties and biological function, therefore, fibronectin from different organisms may be interchangeable (33,34,37).…”

“…Fibronectin has many different subunits which are the expression products of the same gene but different in the RNA splicing after transcription and thus different mRNA are produced (38). Fibronectin is widely distributed in hematoma, the surface of numerous types of cells and extracellular matrix (36). Fibronectin is crucially involved in cell adhesion, migration, differentiation and functions.…”

STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury

“…One week after the last injection, mice were anesthetized (ketamine/xylazine, 100 mg/15 mg/kg i.p.) and received contusive SCI as previously described (Lee and Lee, 2013, Zhu et al, 2015). Mice received a T8 laminectomy, and the spinal column stabilized using spinal clamps, and then received a moderate (75 kDyne) SCI using an Infinite Horizons impactor device (Precision Systems and Instrumentation, LLC).…”

“Targeting astrocytes in CNS injury and disease: A translational research approach”

“…Later on, processes of the elongated reactive astrocytes near the lesion edge adjacent to the fibroblast-like pericyte population form mesh-like structures that lead to scar formation. The scar itself contains two distinct regions: the lesion core, which is comprised mostly of NG2 glia (Busch et al, 2010; Filous et al, 2014), fibroblasts/pericytes (Zhu et al, 2015), and macrophages (Busch et al, 2009; Horn et al, 2008) and the penumbra, which is formed primarily by reactive astrocytes and activated microglia (Evans et al, 2014). NG2 glia are also found immediately adjacent to the lesion core, with the ability to form a bridge into the center of the lesion (Busch et al, 2010; Cregg et al, 2014; Filous et al, 2014).…”