Dynamic role of kallikrein 6 in traumatic spinal cord injury

Isobel A Scarisbrick, P. Sabharwal, H. Cruz, N. Larsen, A. G. Vandell, S. I. Blaber, S. Ameenuddin, L. M. Papke, M. G. Fehlings, R. K. Reeves, M. Blaber, Anthony John Windebank, M. Rodriguez

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration. Examination of K6 expression following contusion injury to the adult rat cord, and in cases of human traumatic SCI, indicated significant elevations at acute and chronic time points, not only at the injury site but also in cord segments above and below. Elevations in K6 were particularly prominent in macrophages, microglia and reactive astrocytes. To determine potential effects of elevated K6 on the regeneration environment, the ability of neurons to adhere to and extend processes on substrata which had been exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6-mediated proteolytic digestion of a growth-facilitatory substrate, laminin, significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a growth-inhibitory substrate, aggrecan, significantly increased neurite extension and cell adherence. These data support the hypothesis that K6 enzymatic cascades mediate events secondary to spinal cord trauma, including dynamic modification of the capacity for axon outgrowth.

Original languageEnglish (US)
Pages (from-to)1457-1469
Number of pages13
JournalEuropean Journal of Neuroscience
Volume24
Issue number5
DOIs
StatePublished - Sep 2006

Fingerprint

Kallikreins
Spinal Cord Injuries
Regeneration
Wounds and Injuries
Central Nervous System
Neurons
Aggrecans
Contusions
Oligodendroglia
Microglia
Serine Proteases
Laminin
Neurites
Growth
Astrocytes
Trypsin
Digestion
Hydrolysis
Macrophages

Keywords

  • Aggrecan
  • Human
  • Laminin
  • Neurite outgrowth
  • Rat
  • Serine protease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Scarisbrick, I. A., Sabharwal, P., Cruz, H., Larsen, N., Vandell, A. G., Blaber, S. I., ... Rodriguez, M. (2006). Dynamic role of kallikrein 6 in traumatic spinal cord injury. European Journal of Neuroscience, 24(5), 1457-1469. https://doi.org/10.1111/j.1460-9568.2006.05021.x

Dynamic role of kallikrein 6 in traumatic spinal cord injury. / Scarisbrick, Isobel A; Sabharwal, P.; Cruz, H.; Larsen, N.; Vandell, A. G.; Blaber, S. I.; Ameenuddin, S.; Papke, L. M.; Fehlings, M. G.; Reeves, R. K.; Blaber, M.; Windebank, Anthony John; Rodriguez, M.

In: European Journal of Neuroscience, Vol. 24, No. 5, 09.2006, p. 1457-1469.

Research output: Contribution to journalArticle

Scarisbrick, IA, Sabharwal, P, Cruz, H, Larsen, N, Vandell, AG, Blaber, SI, Ameenuddin, S, Papke, LM, Fehlings, MG, Reeves, RK, Blaber, M, Windebank, AJ & Rodriguez, M 2006, 'Dynamic role of kallikrein 6 in traumatic spinal cord injury', European Journal of Neuroscience, vol. 24, no. 5, pp. 1457-1469. https://doi.org/10.1111/j.1460-9568.2006.05021.x
Scarisbrick, Isobel A ; Sabharwal, P. ; Cruz, H. ; Larsen, N. ; Vandell, A. G. ; Blaber, S. I. ; Ameenuddin, S. ; Papke, L. M. ; Fehlings, M. G. ; Reeves, R. K. ; Blaber, M. ; Windebank, Anthony John ; Rodriguez, M. / Dynamic role of kallikrein 6 in traumatic spinal cord injury. In: European Journal of Neuroscience. 2006 ; Vol. 24, No. 5. pp. 1457-1469.
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