Transforming growth factor-β1 enhances expression of brain-derived neurotrophic factor and its receptor, TrkB, in neurons cultured from rat cerebral cortex

✍ Scribed by Ayako Sometani; Hiroshige Kataoka; Atsumi Nitta; Hidefumi Fukumitsu; Hiroshi Nomoto; Shoei Furukawa

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 168 KB
• Volume: 66
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.1229

✦ Synopsis

Abstract

The effects of transforming growth factor (TGF)‐β1 on expression of brain‐derived neurotrophic factor (BDNF) and its high‐affinity receptor, TrkB, in neurons cultured from the cerebral cortex of 18‐day‐old embryonic rats were examined. BDNF mRNA was significantly increased from 24–48 hr after the TGF‐β1 treatment over 20 ng/ml. Accumulation of BDNF protein in the culture medium was also potentiated by TGF‐β1, although the intracellular content of BDNF was nearly unchanged. The enhancement of BDNF mRNA expression was suppressed by the co‐presence of decorin, a small TGF‐β‐binding proteoglycan that inhibits the biological activities of TGF‐βs. mRNA expression of full‐length TrkB, the bioactive high‐affinity receptor for BDNF, was also upregulated after treatment with TGF‐β1. These observations suggest that: 1) TGF‐β1 potentiates BDNF/TrkB autocrine or local paracrine system; and 2) the neurotrophic activity of TGF‐β1 is partly responsible for the BDNF induced by TGF‐β1 itself. To test this latter possibility, we examined the neuronal survival activity of TGF‐β1 with or without K252a, a selective inhibitor of Trk family tyrosine kinases. TGF‐β1 significantly enhanced neuronal survival, but the co‐presence of K252a completely suppressed the activity, demonstrating the involvement of Trk receptor signaling in TGF‐β1‐mediated neuronal survival in cultured rat cortical neurons. These results seem to be in line with recent findings by other investigators that some neurotrophic factors including BDNF require TGF‐βs as a cofactor to exert their neurotrophic activities. J. Neurosci. Res. 66:369–376, 2001. © 2001 Wiley‐Liss, Inc.