Research article

Expression patterns and different subcellular localization of the growth factors HDGF (hepatoma-derived growth factor) and HRP-3 (HDGF-related protein-3) suggest functions in addition to their mitogenic activity

Mekky M. ABOUZIED, Stephan L. BAADER, Frank DIETZ, Joachim KAPPLER, Volkmar GIESELMANN, Sebastian FRANKEN


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.

  • brain development
  • cell proliferation
  • HDGF-related protein-3 (HRP-3)
  • hepatoma-derived growth factor (HDGF)
  • nuclear localization
  • survival factor


  • Abbreviations used: EGL, external granule cell layer; GST, glutathione S-transferase; HATH, homologous to N-terminus (‘amino-terminus’) of HDGF; HDGF, hepatoma-derived growth factor; HRP, HDGF-related protein; LEDGF, lens epithelium-derived growth factor; MALDI-TOF MS, matrix-assisted laser-desorption ionization–time of flight MS.