KIAA1199 expression and hyaluronan degradation colocalize in multiple sclerosis lesions. (31st July 2018)

• Record Type: Journal Article
• Authors: Marella, Mathieu; Jadin, Laurence; Keller, Gilbert A; Sugarman, Barry J; Frost, Gregory I; Shepard, H Michael
• Is Part Of: Glycobiology. Volume 28:Number 12(2018)
• Page Start: 958
• Page End: 967
• Publication Date: 2018-07-31
• Subjects: Astrocyte -- CEMIP -- hyaluronan -- KIAA1199 -- multiple sclerosis; Glycoproteins -- Periodicals; Glycolipids -- Periodicals; Glycoconjugates -- Periodicals; 572.567
• DOI: 10.1093/glycob/cwy064
• Languages: English
• ISSNs: 0959-6658

Abstract

Abstract: Modification of hyaluronan (HA) accumulation has been shown to play a key role in regulating inflammatory processes linked to the progression of multiple sclerosis (MS). The aim of this study was to characterize the enzymatic activity involved in HA degradation observed within focal demyelinating lesions in the experimental autoimmune encephalomyelitis (EAE) animal model. EAE was induced in 3-month-old female C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein 33–35 (MOG33–35) peptide. The mice were monitored for 21 days. Formalin-fixed paraffin-embedded tissue from control and EAE mice were labeled with an immunoadhesin against HA, antibodies against KIAA1199 and glial fibrillary acidic protein, a marker for astrocytes. In situ hybridization was conducted using a KIAA1199 nucleic acid probe. In histologic sections of spinal cord from EAE mice, abnormal HA accumulation was observed in the close vicinity of the affected areas, whereas HA was totally degraded within the focal loci of damaged tissue. KIAA1199 immunoreactivity was exclusively associated with focal loci in damaged white columns of the spinal cord. KIAA1199 was mainly expressed by activated astrocytes that invaded damaged tissue. Similar findings were observed in tissue from an MS patient. Here, we show that KIAA1199, a protein that plays a role in a HA degradation pathway independent of the canonical hyaluronidases such as PH20, is specifically expressed in tissue lesions in which HA is degraded. KIAA1199 expression by activated astrocytes may explain the focal HA degradation observed during progression of MS and could represent a possible new therapeutic target.