Transforming Growth Factor-β1 in the Rat Brain: Increase after Injury and Inhibition of Astrocyte Proliferation

Transforming growth factor-β1 (TGF-β1) has been shown to up-regulate the synthesis of nerve growth factor (NGF) in cultured rat astrocytes and in neonatal brain in vivo (Lindholm, D., B. Hengerer, F. Zafra, and H. Thoenen. 1990. NeuroReport. 1:9-12). Here we show that mRNA encoding TGF-β1 increased...

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Bibliographic Details
Published in:The Journal of cell biology 1992-04, Vol.117 (2), p.395-400
Main Authors: Lindholm, Dan, Castrén, Eero, Kiefer, Reinhard, Zafra, Francisco, Thoenen, Hans
Format: Article
Language:English
Subjects:
Astrocytes
Biological and medical sciences
Brain
Cell growth
Cell physiology
Cells
Fundamental and applied biological sciences. Psychology
In situ hybridization
Macrophages
Messenger RNA
Molecular and cellular biology
Neuroglia
Neurons
Responses to growth factors, tumor promotors, other factors
RNA
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Summary:Transforming growth factor-β1 (TGF-β1) has been shown to up-regulate the synthesis of nerve growth factor (NGF) in cultured rat astrocytes and in neonatal brain in vivo (Lindholm, D., B. Hengerer, F. Zafra, and H. Thoenen. 1990. NeuroReport. 1:9-12). Here we show that mRNA encoding TGF-β1 increased in rat cerebral cortex after a penetrating brain injury. The level of NGF mRNA is also transiently increased after the brain trauma, whereas that of brain-derived neurotrophic factor remained unchanged. In situ hybridization experiments showed a strong expression of TGF-β1 4 d after the lesion in cells within and in the vicinity of the wound. Staining of adjacent sections with OX-42 antibodies, specific for macrophages and microglia/brain macrophages, revealed a similar pattern of positive cells, suggesting that invading macrophages, and perhaps reactive microglia, are the source of TGF-β1 in injured brain. Both astrocytes and microglia express TGF-β1 in culture, and TGF-β1 mRNA levels in astrocytes are increased by various growth factors, including FGF, EGF, and TGF-β itself. TGF-β1 is a strong inhibitor of astrocyte proliferation and suppresses the mitotic effects of FGF and EGF on astrocytes. The present results indicate that TGF-β1 expressed in the lesioned brain plays a role in nerve regeneration by stimulating NGF production and by controlling the extent of astrocyte proliferation and scar formation.
ISSN:0021-9525
1540-8140