Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation.
Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 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-beta 1 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-beta 1 in injured brain. Both astrocytes and microglia express TGF-beta 1 in culture, and TGF-beta 1 mRNA levels in astrocytes are increased by various growth factors, including FGF, EGF, and TGF-beta itself. TGF-beta 1 is a strong inhibitor of astrocyte proliferation and suppresses the mitotic effects of FGF and EGF on astrocytes. The present results indicate that TGF-beta 1 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.
Lindholm
D
D
Department of Neurochemistry, Max-Planck-Institute for Psychiatry, Planegg-Martinsried, Federal Republic of Germany.
Castrén
E
E
Kiefer
R
R
Zafra
F
F
Thoenen
H
H
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta