Premium
Up‐regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1
Author(s) -
Buisson Alain,
Nicole Olivier,
Docagne Fabian,
Sartelet Hervé,
Mackenzie Eric T.,
Vivien Denis
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.15.1683
Subject(s) - neuroprotection , serine protease , microbiology and biotechnology , transforming growth factor , chemistry , neuroscience , protease , pharmacology , biology , biochemistry , enzyme
Serine proteases play a key role in the fundamental biology of the central nervous system (CNS), and recent data suggest their involvement in the pathophysiology of neurodegenerative diseases. Little is known about the physiological regulation of these proteases in the CNS. Among the multiple growth factors present in the brain, transforming growth factor β1 (TGF‐β1) has been described as an injury‐related growth factor. However, its beneficial or deleterious role remains unclear. In the present study, we investigated the influence of TGF‐β1 in apoptosis and necrosis, two mechanisms involved in ischemic neuronal death. We show that TGF‐β1 exerts a neuroprotective role restricted to necrosis induced by N‐methyl‐D‐aspartate. This effect is observable only in the obligatory presence of TGF‐β1‐responsive astrocytes. We demonstrate that this neuroprotective activity is mediated through an up‐regulation of a serine protease inhibitor (PAI‐1) in astrocytes. These results underline the involvement of serine proteases and extracellular matrix components such as the PAI‐1/t‐PA axis in the excitotoxic cascade. Moreover, regardless of the underlying mechanisms of t‐PA involvement in excitotoxic injury, our observations might warn against the use of tissular plasminogen activator as an alternative therapy for the treatment of hypoxic‐ischemic injury in the brain.—Buisson, A., Nicole, O., Docagne, F., Sartelet, H., MacKenzie, E. T., Vivien, D. Up‐regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor β1. FASEB J. 12, 1683–1691 (1998)