Transforming growth factor beta 1 and fibronectin messenger RNA in rat brain: responses to injury and cell-type localization.
Transforming growth factor-beta 1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the schedule of changes, regional distribution, and cellular localization of striatal transforming growth factor-beta 1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal cortex ablation. Frontal cortex ablation induced striatal transforming growth factor-beta 1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortico-striatal afferent fibers. Within three days post-lesioning, transforming growth factor-beta 1 messenger RNA was localized at the cortical wound. By 10 days, the anatomical site of transforming growth factor-beta 1 messenger RNA expression shifted to the dorsal half of the deafferented striatum and co-localized with OX-42+ immunostained microglia-macrophage at the site of degenerating afferent terminals. Similarly, fibronectin messenger RNA also shifted from the cortical wound to the deafferented striatum by 10 days post-lesioning. Fibronectin messenger RNA was localized to glial fibrillary acidic protein+ immunostained astrocytes surrounding degenerating corticostriatal afferents. Infusion of transforming growth factor-beta 1 peptide elevated striatal and cortical fibronectin messenger RNA. These findings suggest that microglia-macrophage associated with degenerating afferent fibres can upregulate transforming growth factor-beta 1 messenger RNA and may influence fibronectin messenger RNA synthesis in reactive astrocytes. This study suggests that transforming growth factor-beta 1 has a role in controlling extracellular matrix synthesis following brain injury, which is analogous to that in peripheral wound healing.
Pasinetti
G M
GM
Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Nichols
N R
NR
Tocco
G
G
Morgan
T
T
Laping
N
N
Finch
C E
CE
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D016622:Silver Staining; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000494:pharmacology
D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA