Pleiotrophin Human

Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in the rat brain around birth and as a mitogen toward fibroblasts isolated from bovine uterus tissue . It is structurally related to midkine and retinoic acid-induced heparin-binding protein . Together with midkine, these growth factors constitute a family of developmentally regulated secreted heparin-binding proteins known as the neurite growth-promoting factor (NEGF) family .

During embryonic and early postnatal development, pleiotrophin is expressed in the central and peripheral nervous systems and several non-neural tissues, including the lung, kidney, gut, and bone . In the adult central nervous system, pleiotrophin is expressed in an activity-dependent manner in the hippocampus, where it can suppress long-term potentiation induction . Its expression is low in other areas of the adult brain but can be induced by ischemic insults or targeted neuronal damage .

Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis . High serum levels of pleiotrophin are associated with a variety of solid tumors and multiple myeloma .

Pleiotrophin binds to cell-surface nucleolin as a low-affinity receptor, which can inhibit HIV infection . It also interacts with protein tyrosine phosphatase beta/zeta (RPTPβ/ζ), which is involved in its signaling pathways . The interaction between pleiotrophin and nucleolin has functional significance, as it can influence endothelial cell migration and angiogenesis .

Pleiotrophin’s role in tumor growth and angiogenesis makes it a potential target for cancer therapy . Its expression in various tissues during development and in response to injury suggests it may have therapeutic potential in regenerative medicine and neuroprotection .