Suzuki Yoshinori, Funakoshi Hiroshi, Machide Mitsuru, Matsumoto Kunio, Nakamura Toshikazu
Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Biomed Res. 2008 Apr;29(2):77-84. doi: 10.2220/biomedres.29.77.
HGF-like protein (HLP)/macrophage stimulating protein (MSP) is the only structural relative of hepatocyte growth factor (HGF), and is involved in the regulation of peripheral macrophage activation. However, the actions of HLP in microglia, a species of macrophage in the nervous system, which is closely involved in the neural degeneration and regeneration, is not yet understood. This study found that Ron, the receptor for HLP, is expressed in primary microglia using RT-PCR, immunocytochemical staining and Western blotting, and, thus, sought to elucidate the function of HLP on the primary microglia. HLP promoted microglial migration without affecting cell survival and proliferation. Furthermore, real-time quantitative RT-PCR analysis revealed that HLP greatly increased the mRNA of inflammatory cytokines, including IL-6 and GM-CSF, and iNOS. These findings provide the first evidence that HLP has the potential to modulate inflammatory actions of microglia, which proposes novel aspects for the process of degeneration and/or regeneration of the brain.
肝细胞生长因子样蛋白（HLP）/巨噬细胞刺激蛋白（MSP）是肝细胞生长因子（HGF）唯一的结构相关蛋白，参与外周巨噬细胞活化的调节。然而，HLP在小胶质细胞（一种在神经系统中密切参与神经退变和再生的巨噬细胞）中的作用尚不清楚。本研究通过逆转录聚合酶链反应（RT-PCR）、免疫细胞化学染色和蛋白质印迹法发现，HLP的受体Ron在原代小胶质细胞中表达，因此试图阐明HLP对原代小胶质细胞的功能。HLP促进小胶质细胞迁移，而不影响细胞存活和增殖。此外，实时定量RT-PCR分析显示，HLP显著增加了包括白细胞介素-6（IL-6）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和诱导型一氧化氮合酶（iNOS）在内的炎性细胞因子的信使核糖核酸（mRNA）。这些发现首次证明HLP具有调节小胶质细胞炎性作用的潜力，这为脑退变和/或再生过程提出了新的方面。
