Expression of plasminogen activator inhibitor-1 and protease nexin-1 in human astrocytes: Response to injury-related factors

Journal of Neuroscience Research
K HultmanAnna Tjärnlund-Wolf

Abstract

Astrocytes play a diverse role in central nervous system (CNS) injury. Production of the serine protease inhibitors (serpins) plasminogen activator inhibitor-1 (PAI-1) and protease nexin-1 (PN-1) by astrocytes may counterbalance excessive serine protease activity associated with CNS pathologies such as ischemic stroke. Knowledge regarding the regulation of these genes in the brain is limited, so the objective of the present study was to characterize the effects of injury-related factors on serpin expression in human astrocytes. Native human astrocytes were exposed to hypoxia or cytokines, including interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-10, transforming growth factor-alpha (TGF-alpha), and TGF-beta for 0-20 hr. Serpin mRNA expression and protein secretion were determined by real-time RT-PCR and ELISA, respectively. Localization of PAI-1 and PN-1 in human brain tissue was examined by immunohistochemistry. Hypoxia and all assayed cytokines induced a significant increase in PAI-1 expression, whereas prolonged treatment with IL-1beta or TNF-alpha resulted in a significant down-regulation. The most pronounced induction of both PAI-1 and PN-1 was observed following early treatment with TGF-alpha. ...Continue Reading

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Citations

Aug 11, 2012·Stroke; a Journal of Cerebral Circulation·Anna Tjärnlund-WolfXiaoying Wang
Jul 4, 2012·Journal of Neuroinflammation·Hyejin JeonKyoungho Suk
Jan 11, 2014·Neuroscience Letters·Milos PeknyMarcela Pekna
Jul 3, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Delphine GomezJean-Baptiste Michel
Jan 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Rachel E BennettBradley T Hyman
Apr 5, 2020·Journal of Clinical Medicine·Jordan R YaronAlexandra R Lucas

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