title: Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin.
abstract: 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 glomerular deposition of predominantly multimeric fibronectin (Fn). The molecular mechanism 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.
authors.affiliation: Section on Developmental Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development (NICHD), National Insitutes of Health (NIH), Bethesda, MD 20892-1830, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: G C
authors.initials: GC
authors.lastname: Kundu
authors.forename: C J
authors.initials: CJ
authors.lastname: Yuan
authors.forename: J M
authors.initials: JM
authors.lastname: Ward
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.forename: F
authors.initials: F
authors.lastname: DeMayo
authors.forename: H
authors.initials: H
authors.lastname: Westphal
authors.forename: A B
authors.initials: AB
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005353:Fibronectins / Q000378:metabolism*; D018390:Gene Targeting; D006801:Humans; D007674:Kidney Diseases / Q000196:embryology / Q000235:genetics / Q000473:pathology; D007678:Kidney Glomerulus / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D014598:Uteroglobin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D005353:Fibronectins; D014598:Uteroglobin