Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin

Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glo-merular deposition of predominantly multimeric fibronectin (Fn). The molecular mech-anism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation, which is required for abnormal tissue deposition. Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease. Blastokinin (1) or UG (2) is a steroid-inducible, evolutionarily conserved, ho-modimeric secreted protein with many bio-logical activities including the ability to inhibit soluble phospholipase A2 (sPLA2) activity, inflammation, and chemotaxis o