Uteroglobin: a novel cytokine?

Blastokinin or uteroglobin (UG) is a steroid-inducible, evolutionarily cons erved, multifunctional protein secreted by the mucosal epithelia of virtual ly all mammals. It is present in the blood and in other body fluids includi ng urine. An antigen immunoreactive to UG antibody is also detectable in th e mucosal epithelia of all vertebrates. UG-binding proteins (putative recep tor), expressed on several normal and cancer cell types, have been characte rized. The human UG gene is mapped to chromosome 11q(12.2-13.1), a region t hat is frequently rearranged or deleted in many cancers. The generation of UG knockout mice revealed that disruption of this gene causes: (i) severe r enal disease due to an abnormal deposition of fibronectin and collagen in t he glomeruli; (ii) predisposition to a high incidence of malignancies; and (iii) a lack of polychlorinated biphenyl binding and increased oxygen toxic ity in the lungs. The mechanism(s) of UG action is likely to be even more c omplex as it also functions via a putative receptor-mediated pathway that h as not yet been clearly defined. Molecular characterization of the UG recep tor and signal transduction via this receptor pathway may show that this pr otein belongs to a novel cytokine/chemokine family.