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Kallikrein 6 is a Novel Molecular Trigger of Reactive Astrogliosis

Title: Kallikrein 6 is a Novel Molecular Trigger of Reactive Astrogliosis.
Name(s): Scarisbrick, Isobel, author
Radulovic, Maja, author
Burda, Joshua, author
Larson, Nadya, author
Blaber, Sachiko, author
Giannini, Caterina, author
Blaber, Michael, author
Vandell, Alexander, author
Type of Resource: text
Genre: text
Issuance: serial
Date Issued: 2012
Physical Form: computer
Physical Form: online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Kallikrein-related peptidase 6 (KLK6) is a trypsin-like serine protease upregulated at sites of central nervous system (CNS) injury, including de novo expression by reactive astrocytes, yet its physiological actions are largely undefined. Taken with recent evidence that KLK6 activates G-protein-coupled protease-activated receptors (PARs), we hypothesized that injury-induced elevations in KLK6 contribute to the development of astrogliosis and that this occurs in a PAR-dependent fashion. Using primary murine astrocytes and the Neu7 astrocyte cell line, we show that KLK6 causes astrocytes to transform from an epitheliod to a stellate morphology and to secrete interleukin 6 (IL-6). By contrast, KLK6 reduced expression of glial fibrillary acidic protein (GFAP). The stellation-promoting activities of KLK6 were shown to be dependent on activation of the thrombin receptor, PAR1, as a PAR1-specific inhibitor, SCH79797, blocked KLK6-induced morphological changes. The ability of KLK6 to promote astrocyte stellation was also shown to be linked to activation of protein kinase C (PKC). These studies indicate that KLK6 is positioned to serve as a molecular trigger of select physiological processes involved in the development of astrogliosis and that this is likely to occur at least in part by activation of the G-protein-coupled receptor, PAR1.
Identifier: FSU_migr_biomed_faculty_publications-0030 (IID), 10.1515/hsz-2011-0241 (DOI)
Keywords: astrocyte, protease activated receptor, spinal cord injury, multiple sclerosis, glioblastoma, GFAP, IL-6
Note: Originally published in Biological Chemistry
Citation: Scarisbrick, I., Radulovic, M., Burda, J., Larson, N., Blaber, S., Gianinni, C., Blaber, M. and Vandell, A. (2012). Kallikrein 6 is a Novel Molecular Trigger of Reactive Astrogliosis. Biol. Chem. 393, 355-67. doi: 10.1515/hsz-2011-0241.
Subject(s): Biochemistry
Molecular biology
Developmental biology
Medical sciences
Persistent Link to This Record:
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Biological Chemistry.
Issue: 5, 393