Glcci1 Deficiency Leads to Proteinuria

J Am Soc Nephrol. 2011 Nov;22(11):2037-46. doi: 10.1681/ASN.2010111147. Epub 2011 Sep 23.

Abstract

Unbiased transcriptome profiling and functional genomics approaches identified glucocorticoid-induced transcript 1 (GLCCI1) as being a transcript highly specific for the glomerulus, but its role in glomerular development and disease is unknown. Here, we report that mouse glomeruli express far greater amounts of Glcci1 protein compared with the rest of the kidney. RT-PCR and Western blotting demonstrated that mouse glomerular Glcci1 is approximately 60 kD and localizes to the cytoplasm of podocytes in mature glomeruli. In the fetal kidney, intense Glcci1 expression occurs at the capillary-loop stage of glomerular development. Using gene knockdown in zebrafish with morpholinos, morphants lacking Glcci1 function had collapsed glomeruli with foot-process effacement. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of the selective glomerular permeability filter. Taken together, these data suggest that Glcci1 promotes the normal development and maintenance of podocyte structure and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoplasm / metabolism
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Glucocorticoids / pharmacology
  • Kidney Glomerulus / abnormalities
  • Kidney Glomerulus / physiopathology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Oligonucleotides, Antisense / pharmacology
  • Podocytes / physiology*
  • Pronephros / abnormalities
  • Pronephros / physiopathology*
  • Proteinuria / metabolism*
  • Proteinuria / pathology
  • Proteinuria / physiopathology*
  • Rabbits
  • Receptors, Glucocorticoid / deficiency*
  • Receptors, Glucocorticoid / genetics
  • Zebrafish
  • Zebrafish Proteins

Substances

  • Glucocorticoids
  • Oligonucleotides, Antisense
  • Receptors, Glucocorticoid
  • Zebrafish Proteins
  • glcci1a protein, zebrafish
  • glucocorticoid-induced transcript 1 protein, mouse
  • Dexamethasone