The SGP-2 gene is developmentally regulated in the mouse kidney and abnormally expressed in collecting duct cysts in polycystic kidney disease.
Sulfated glycoprotein-2 (SGP-2) is a secreted, dimeric, glycosylated protein synthesized by a number of different epithelial cell types. Although its function is not yet understood, SGP-2 has been hypothesized to be involved in such diverse processes as the promotion of cell-cell interactions, spermatogenesis, modulation of the complement system, and programmed cell death. We have now found that the SGP-2 gene is developmentally regulated in the mouse kidney. SGP-2 gene expression is first detected in the condensing nephrogenic mesenchyme and is subsequently down-regulated during the maturation of the glomerular epithelia, proximal tubules, and collecting ducts. SGP-2 continues to be expressed in the mature kidney in distal tubules and in the urothelial lining of the calyx and papilla. We have also examined the expression of the SGP-2 gene in polycystic kidneys of the C57BL/6J-cpk mouse, a model of autosomal recessive polycystic kidney disease in which there is development of epithelial-lined cysts arising primarily from the collecting duct system. Abnormally high levels of SGP-2 mRNA were found in the cyst wall epithelium of polycystic kidneys. The expression of the SGP-2 gene in normal development suggests that it plays a role in differentiating epithelial structures; and the abnormally high levels of SGP-2 gene expression in polycystic kidneys suggests that the cells lining cysts are not fully differentiated. It is possible, therefore, that polycystic kidney disease is caused by a defective developmental process in which there is a delay in terminal differentiation.
Harding
M A
MA
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66103.
Chadwick
L J
LJ
Gattone
V H
VH
Calvet
J P
JP
D000818:Animals; D051152:Clusterin; D004848:Epithelium / Q000737:chemistry / Q000254:growth & development; D005786:Gene Expression Regulation; D005796:Genes; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D007668:Kidney / Q000254:growth & development*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000254:growth & development; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000254:growth & development* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D018832:Molecular Chaperones; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000503:physiopathology
C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones