Pleiotrophin (PTN) also known as heparin-binding brain mitogen (HBBM) or heparin-binding growth factor 8 (HBGF-8) or neurite growth-promoting factor 1 (NEGF1) or heparin affinity regulatory peptide (HARP) or heparin binding growth associated molecule (HB-GAM) is a protein that in humans is encoded by the PTN gene.[5] Pleiotrophin 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[6] and as a mitogen toward fibroblasts isolated from bovine uterus tissue.[7] Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins[8] 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.[9] Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis.[10] In the adult central nervous system, pleiotrophin is expressed in an activity-dependent manner in the hippocampus[11][12] where it can suppress long term potentiation induction.[13] Pleiotrophin expression is low in other areas of the adult brain, but it can be induced by ischemic insults.[14][15] or targeted neuronal damaged in the entorhinal cortex or in the substantia nigra pars compacta.
Pleiotrophin binds to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.[16]