title: Clusterin expression by astrocytes is influenced by transforming growth factor beta 1 and heterotypic cell interactions.
abstract: This study characterizes the effect of transforming growth factor (TGF) beta 1 on clusterin expression in rat brain cells. 24 h after an acute unilateral intracerebroventricular infusion of TGF-beta 1, clusterin mRNA prevalence was increased in astrocytes that contained immunoreactive (IR) glial fibrillary acidic protein (GFAP). TGF-beta 1 selectively induced clusterin mRNA in astrocytes, as no clusterin mRNA was detected in neurons, oligodendrocytes, or microglia. TGF-beta 1 induced a bilateral increase in clusterin mRNA per astrocyte. Astrocyte hypertrophy (GFAP-IR area) was only increased on the ipsilateral side. In pure astrocyte cultures, TGF-beta 1 (200 pM) decreased clusterin mRNA levels and the rate of clusterin RNA transcription. However, in cultures of astrocytes that contained microglia and oligodendrocytes (mixed glia cultures), TGF-beta 1 caused a dose-dependent increase in astrocytic clusterin mRNA levels. The astrocytes that responded to TGF-beta 1 included two GFAP-IR subtypes, type 1 and 2. TGF-beta 1 increased clusterin protein in the conditioned medium from cultured glia, in either monotypic or mixed glial cultures. Thus, TGF-beta 1 and heterotypic cell interactions influence clusterin expression by astrocytes and may be important to the role of clusterin in multiple sclerosis, AIDS, and Alzheimer's disease.
authors.affiliation: Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Morgan
authors.forename: N J
authors.initials: NJ
authors.lastname: Laping
authors.forename: I
authors.initials: I
authors.lastname: Rozovsky
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.forename: T H
authors.initials: TH
authors.lastname: Hogan
authors.forename: C E
authors.initials: CE
authors.lastname: Finch
authors.forename: G M
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D051152:Clusterin; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006023:Glycoproteins / Q000096:biosynthesis*; D007263:Infusions, Parenteral; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D051152:Clusterin; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta