Pleiotrophin

Pleiotrophin or Neurite Growth-promoting Factor 1 (NEGF1), also called Heparin Affin Regulatory Peptide (HARP) or Heparin Binding Growth associated molecule (HB-GAM) is an 18-kDa growth factor that has a high affinity for heparin. It is structurally related to midkine and retinoic acid induced heparin-binding protein.

Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in rat brain around birth and as a mitogen toward fibroblasts isolated from bovine uterus tissue. Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins (Laaroubi et al., 1995) now known as the Neurite Growth-promoting Factor (NEGF) family. During embryonic and early postnatal development, Pleiotrophin is expressed in the central and peripheral nervous system and also in several non-neural tissues, notably lung, kidney, gut and bone (Vanderwinden et al., 1992). Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis (Kadomatsu and Muramatsu, 2004). In the adult central nervous system Pleiotrophin is expressed in an activity-dependent manner in the hippocampus (Wanaka et al., 1993; Lauri et al., 1996), where it can suppress long term potentiation induction (Pavlov et al., 2002). Pleiotrophin expression is low in other areas of the adult brain, but it can be induced by ischemic insults (Takeda et al., 1995; Yeh et al., 1998).