Abouzied Mekky M, Baader Stephan L, Dietz Frank, Kappler Joachim, Gieselmann Volkmar, Franken Sebastian
Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany.
Biochem J. 2004 Feb 15;378(Pt 1):169-76. doi: 10.1042/BJ20030916.
HDGF (hepatoma-derived growth factor) and the HRPs (HDGF-related proteins) comprise a family of six proteins which display high identity in their N-terminus, but differ at the C-terminus. Here we investigate the patterns of expression of HDGF and HRP-3, by generating antisera specifically recognizing each growth factor. Whereas HRP-3 protein is expressed only in brain, HDGF can be found in a broad range of tissues, with highest levels in brain, testis, lung and spleen. The expression of HDGF and HRP-3 was found to be regulated during brain development, with highest levels around birth, followed by a decline until postnatal day 9. Interestingly, expression of HRP-3 increases again in adult brain. In situ hybridization and immunohistochemistry of cerebellar, cerebral and hippocampal brain slices showed that expression of both growth factors is not limited to areas of high proliferative activity. Both mRNAs and proteins are expressed in neuronal as well as glial cells. Immunocytochemistry of cultured neocortical neurons revealed that HDGF and HRP-3 can be found in the nucleus as well as the cytoplasm. HDGF is restricted to the neuronal soma, whereas HRP-3 can also be found in neurites. Thus the expression of HDGF and HRP-3 in differentiated cells, post-mitotic neurons and primary cultures of rat neocortex points to functions in brain that might not be limited to proliferation. In addition, their simultaneous expression in the same cell and their different subcellular localization in cultured neurons suggest different functions of HDGF and HRP-3 within single cells.
肝癌衍生生长因子（HDGF）和HDGF相关蛋白（HRPs）构成了一个由六种蛋白质组成的家族，它们在N端具有高度同源性，但C端有所不同。在此，我们通过制备特异性识别每种生长因子的抗血清，研究了HDGF和HRP-3的表达模式。HRP-3蛋白仅在脑中表达，而HDGF在多种组织中都能检测到，在脑、睾丸、肺和脾脏中的表达水平最高。研究发现，HDGF和HRP-3的表达在脑发育过程中受到调控，出生前后表达水平最高，随后下降，直至出生后第9天。有趣的是，HRP-3在成体脑中的表达再次升高。对小脑、大脑和海马脑片进行原位杂交和免疫组织化学分析表明，这两种生长因子的表达并不局限于高增殖活性区域。mRNA和蛋白质在神经元和神经胶质细胞中均有表达。对培养的新皮质神经元进行免疫细胞化学分析显示，HDGF和HRP-3在细胞核和细胞质中均能检测到。HDGF局限于神经元胞体，而HRP-3在神经突中也能检测到。因此，HDGF和HRP-3在分化细胞、有丝分裂后神经元以及大鼠新皮质原代培养物中的表达表明它们在脑中的功能可能不限于增殖。此外，它们在同一细胞中的同时表达以及在培养神经元中不同的亚细胞定位表明HDGF和HRP-3在单个细胞中具有不同的功能。
