Shear stress alters the expression of myelin‐associated glycoprotein (MAG) and myelin basic protein (MBP) in Schwann cells

Abstract

Schwann cells within a peripheral nerve respond robustly after a n axonal injury. Recent results have revealed that Schwann cells undergo concurrent proliferation and apoptosis after a chronic nerve injury that is independent of axonal pathology. Although the exact nature of the stimulus that produces this Schwann cell response remains unknown, we postulated that this response may be triggered directly by mechanical stimuli. Thus, we sought to determine how pure Schwann cells responded to a sustained shear stress in the form of laminar fluid flow by evaluating for proliferation, expression of S-100, myelin-associated glycoprotein (MAG), and myelin basic protein (MBP). Immunohistochemistry demonstrated that the Schwann cells were positive for S-100, MAG, and MBP in greater than 99% of the experimental cells. Stimulated cells also revealed an increased rate of proliferation by as much as 100% (p < .001). The mRNA expression of MAG and MBP was down-regulated by 21% (p < .035) and 18% (p < .015), respectively, in experimental cells from RT-PCR assays. Furthermore, Western blot showed a down-regulation in M A G and MBP protein expression by 29% (p < .035) and 35% (p < .02), respectively. This study provides novel information regarding Schwann cell direct response to this physical stimulus that is not secondary to an axonal injury.

Biophysical stimulation induces demyelination via an integrin‐dependent mechanism

“…24,46 Mechanical loading of SCs alters the expression of genes that permit axonal sprouting, a response observed in later stages of chronic compression injury. 6,47 Our results reported here, colocalizing SCs with the messenger protein Src activated in response to demyelinating biophysical stimuli, further implicate SCs as the prime mediator of CNC injury.…”

“…For example, SCs respond to fluid shear stress in part by proliferating and downregulating myelin-associated genes. 6 We show here that applied hydrostatic pressure triggers SC proliferation and demyelination in a way that is similar to what occurs in vivo despite the maintenance of normal oxygen tension, pH, and available nutrients. These findings provide further evidence that neural tissues can respond directly to pressure.…”

“…Examples include disruption of neuronal microcirculation, 1,2 induction of intracellular hydrostatic pressure gradients, 3 and alteration of cellular substructures. 2 Recent evidence indicates that cells can directly respond to physiological mechanical loading, [4][5][6][7][8] suggesting the existence of a molecular sensor capable of translating mechanical stresses into cellular responses. One particularly attractive candidate for mechanotransduction is the integrin family of heterodimeric transmembrane proteins that bind the extracellular matrix 9,10 and are capable of intracellular signal transduction.…”

The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation

“…NCAM-1, on the other hand, is associated with immature Schwann cells and mature non-myelinating cells and is often down-regulated during myelination [45]. Pro-myelinating Schwann cells also show up-regulation of MAG, P0 and MBP; and a down-regulation of NCAM-1 [46,47].…”

“…As MAG is an important promyelinogenic marker in Schwann cells [47] and an early marker for myelin-differentiation [41], the significant up-regulation of MAG expression in hSCs cultured on electrospun fibers indicates the efficacy of these fibers in driving hSCs towards the pro-myelinating state. Since P0 and MBP are later gene products of myelin-differentiation [41] and PMP22 is associated with myelin formation, the general lack of differences in gene expression between the two-dimensional film and electrospun fibers is not unexpected.…”