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

• 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
• ISSN: 0021-9525; 1540-8140

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.