RGD Reference Report - Oxalate-inducible AMBP gene and its regulatory mechanism in renal tubular epithelial cells. - Rat Genome Database

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Oxalate-inducible AMBP gene and its regulatory mechanism in renal tubular epithelial cells.

Authors: Grewal, JS  Tsai, JY  Khan, SR 
Citation: Grewal JS, etal., Biochem J. 2005 May 1;387(Pt 3):609-16.
RGD ID: 6904219
Pubmed: PMID:15533056   (View Abstract at PubMed)
PMCID: PMC1134990   (View Article at PubMed Central)
DOI: DOI:10.1042/BJ20041465   (Journal Full-text)

The AMBP [A1M (alpha1-microglobulin)/bikunin precursor] gene encodes two plasma glycoproteins: A1M, an immunosuppressive lipocalin, and bikunin, a member of plasma serine proteinase inhibitor family with prototypical Kunitz-type domain. Although previously believed to be constitutively expressed exclusively in liver, the present study demonstrates the induction of this gene by oxalate in porcine proximal tubular LLC-PK1 cells and rat kidney. In liver, the precursor protein is cleaved in the Golgi network by a furin-like enzyme to release constituent proteins, which undergo glycosylation before their export from the cell. In the renal tubular cells, A1M and bikunin co-precipitate, indicating lack of cleavage of the precursor protein. As the expression of the AMBP gene is regulated by A1M-specific cis elements and transcription factors, A1M protein was studied as a representative of AMBP gene expression in renal cells. Oxalate treatment (500 microM) resulted in a time- and dose-dependent induction of A1M protein in LLC-PK1 cells. Of the four transcription factors, HNF-4 (hepatocyte nuclear factor-4) has been reported previously to be a major regulator of AMBP gene expression in liver. Electrophoretic mobility-shift assay, supershift assay, immunoreactivity assay and transfection-based studies showed the presence of an HNF-4 or an HNF-4-like protein in the kidney, which can affect the expression of the AMBP gene. In situ hybridization and immunocytochemical studies showed that the expression of this gene in kidney was mainly restricted to cells lining the renal tubular system.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AMBPHumancalcium oxalate nephrolithiasis  ISOAmbp (Rattus norvegicus)protein:increased expression:urineRGD 
AmbpRatcalcium oxalate nephrolithiasis  IEP protein:increased expression:urineRGD 
AmbpMousecalcium oxalate nephrolithiasis  ISOAmbp (Rattus norvegicus)protein:increased expression:urineRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AmbpRatcell surface  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ambp  (alpha-1-microglobulin/bikunin precursor)

Genes (Mus musculus)
Ambp  (alpha 1 microglobulin/bikunin precursor)

Genes (Homo sapiens)
AMBP  (alpha-1-microglobulin/bikunin precursor)


Additional Information