Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in the spinal cord of PQBP-1 transgenic mice before onset of degeneration.
Hepatoma-derived growth factor (HDGF) is a nuclear protein homologous to the high-mobility group B1 family of proteins. It is known to be released from cells and to act as a trophic factor for dividing cells. In this study HDGF was increased in spinal motor neurons of a mouse model of motor neuron degeneration, polyglutamine-tract-binding protein-1 (PQBP-1) transgenic mice, before onset of degeneration. HDGF promoted neurite extension and survival of spinal motor neurons in primary culture. HDGF repressed cell death of motor neurons after facial nerve section in newborn rats in vivo. We also found a significant increase in p53 in spinal motor neurons of the transgenic mice. p53 bound to a sequence in the upstream of the HDGF gene in a gel mobility shift assay, and promoted gene expression through the cis-element in chloramphenicol acetyl transfer (CAT) assay. Finally, we found that HDGF was increased in CSF of PQBP-1 transgenic mice. Collectively, our results show that HDGF is a novel trophic factor for motor neurons and suggest that it might play a protective role against motor neuron degeneration in PQBP-1 transgenic mice.
Marubuchi
Shigeki
S
Department of Neuropathology, Medical Research Institute and 21st Century Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Tokyo, Japan.
Okuda
Tomohiro
T
Tagawa
Kazuhiko
K
Enokido
Yasushi
Y
Horiuchi
Daisuke
D
Shimokawa
Reiko
R
Tamura
Takuya
T
Qi
Mei-Ling
ML
Eishi
Yoshinobu
Y
Watabe
Kazuhiko
K
Shibata
Masao
M
Nakagawa
Masaya
M
Okazawa
Hitoshi
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology* / Q000503:physiopathology; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009410:Nerve Degeneration / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism
D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C492272:Pqbp1 protein, mouse; D011994:Recombinant Proteins; C051610:hepatoma-derived growth factor