Premium
Retinoids and activation of PKC induce tissue‐type plasminogen activator expression and storage in human astrocytes
Author(s) -
HULTMAN K.,
TJÄRNLUNDWOLF A.,
FISH R. J.,
WILHELMSSON U.,
RYDENHAG B.,
PEKNY M.,
KRUITHOF E. K. O.,
JERN C.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03084.x
Subject(s) - protein kinase c , forskolin , intracellular , secretion , plasminogen activator , activator (genetics) , astrocyte , extracellular , biology , phorbol , gene expression , microbiology and biotechnology , endocrinology , medicine , chemistry , signal transduction , central nervous system , receptor , biochemistry , gene , stimulation
Summary. Background: Emerging data demonstrate important roles for tissue‐type plasminogen activator (t‐PA) in the central nervous system (CNS). In contrast to endothelial cells, little is known about the regulation of t‐PA gene expression and secretion in astrocytes. Objectives: The aims of the present study were to investigate whether t‐PA gene expression is regulated by retinoids and the protein kinase C (PKC) activator phorbol 12‐myristate 13‐acetate (PMA) in human astrocytes, and to study whether t‐PA is stored and subject to regulated release from these cells, as with endothelial cells. Methods: Native human astrocytes were treated with RA and/or PMA. mRNA was quantified by real‐time RT‐PCR and protein secretion determined by ELISA. Intracellular t‐PA immunoreactivity in astrocytes was examined by immunocyto‐ and histochemistry. Results: RA and/or PMA induced a time‐dependent increase in t‐PA mRNA and protein levels in astrocytes, reaching 10‐fold after combined treatment. This was associated with increased amounts of t‐PA storage in intracellular granular structures. Both forskolin and histamine induced regulated release of t‐PA. The presence of t‐PA in reactive astrocytes was confirmed in human brain tissue. Conclusions: These data show that RA and PKC activation induce a strong up‐regulation of t‐PA expression in astrocytes, and increased intracellular storage pools. Moreover, a regulated release of t‐PA can be induced from these cells. This raises the possibility that astrocytes contribute to the regulation of extracellular t‐PA levels in the CNS.