Expression and role of the TGF-β family in glial cells infected with Borna disease virus.
A previous study revealed that the expression of the Borna disease virus (BDV)-encoding phosphoprotein in glial cells was sufficient to induce neurobehavioral abnormalities resembling Borna disease. To evaluate the involvement of the TGF-β family in BDV-induced changes in cell responses by C6 glial cells, we examined the expression levels of the TGF-β family and effects of inhibiting the TGF-β family pathway in BDV-infected C6 (C6BV) cells. The expression of activin βA and BMP7 was markedly increased in BDV-infected cells. Expression of Smad7, a TGF-β family-inducible gene, was increased by BDV infection, and the expression was decreased by treatment with A-83-01 or LDN-193189, inhibitors of the TGF-β/activin or BMP pathway, respectively. These results suggest autocrine effects of activin A and BMP7 in C6BV cells. IGFBP-3 expression was also induced by BDV infection; it was below the detection limit in C6 cells. The expression level of IGFBP-3 was decreased by LDN-193189 in C6BV cells, suggesting that endogenous BMP activity is responsible for IGFBP-3 gene induction. Our results reveal the regulatory expression of genes related to the TGF-β family, and the role of the enhanced BMP pathway in modulating cell responses in BDV-infected glial cells.
Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan. Electronic address: nishino@cc.kyoto-su.ac.jp.
Yoshii
Y
Nishino
Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara 252-5201, Japan.
Masaru
M
Murakami
Division of Applied Biosciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan. Electronic address: mfunaba@kais.kyoto-u.ac.jp.
Masayuki
M
Funaba
D000818:Animals; D001891:Borna disease virus / Q000254:growth & development*; D002460:Cell Line; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions; D009457:Neuroglia / Q000821:virology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016212:Transforming Growth Factor beta
BMP; Borna disease virus; Glial cells; IGFBP-3; TGF-β family