Clusterin expression by astrocytes is influenced by transforming growth factor β1 and heterotypic cell interactions

Abstract

This study characterizes the effect of transforming growth factor (TGF) βl on clusterin expression in rat brain cells. 24 h after an acute unilateral intracerebroventricular infusion of TGF-β1, clusterin mRNA prevalence was increased in astrocytes that contained immunoreactive (IR) glial fibrillary acidic protein (GFAP). TGF-β1 selectively induced clusterin mRNA in astrocytes, as no clusterin mRNA was detected in neurons, oligodendrocytes, or microglia. TGF-β1 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-β1 (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-β1 caused a dose-dependent increase in astrocytic clusterin mRNA levels. The astrocytes that responded to TGF-β1 included two GFAP-IR subtypes, type 1 and 2. TGF-β1 increased clusterin protein in the conditioned medium from cultured glia, in either monotypic or mixed glial cultures. Thus, TGF-β1 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.