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Scientific article
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Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro

Published inNeuropathology and applied neurobiology, vol. 44, no. 4, p. 404-416
Publication date2018-06
First online date2017-05-24
Abstract

Aims: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis.

Methods: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in three independent cohorts (n = 249), analyses its expression pattern in MS lesions (n = 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators.

Results: SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n = 81) and Switzerland (n = 92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC.

Conclusions: Conflicting results of SPARCL-1's differential expression in CSF of three independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level.

eng
Keywords
  • Multiple sclerosis
  • SPARCL-1
  • biomarker
  • blood brain barrier
  • cerebrospinal fluid
  • chronic lesions
  • Adult
  • Biomarkers / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism
  • Disease Progression
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
Affiliation Not a UNIGE publication
Citation (ISO format)
BRIDEL, Claire et al. Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators <i>in vitro</i>. In: Neuropathology and applied neurobiology, 2018, vol. 44, n° 4, p. 404–416. doi: 10.1111/nan.12412
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Identifiers
ISSN of the journal0305-1846
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