title: Distribution and Function of PACAP and Its Receptors in the Healthy and Nephrotic Kidney.
abstract: OBJECTIVE
  Plasma deficiency of pituitary adenylate cyclase-activating polypeptide (PACAP) was recently demonstrated in children with nephrotic syndrome (NS). Previous studies have reported an important protective effect of PACAP on kidney proximal tubules. The aim of this study was to explore the expression of PACAP and its receptors PAC1, VPAC1 and VPAC2 in the healthy and nephrotic kidney and to determine if PACAP has an effect on renal proximal tubular cells exposed to albumin.
  
  
  METHODS
  Expression of PACAP and its receptors was studied using kidney tissue from healthy and nephrotic children, and in 3 human renal cell lines (glomerular microvascular endothelial cells, podocytes and proximal tubular epithelial HK-2 cells). The functionality of the VPAC1 receptor was tested in HK-2 cells, measuring cyclic adenosine monophosphate levels after PACAP exposure. The influence of PACAP on cell viability and transforming growth factor-β1 (TGF-β1) expression was measured in HK-2 cells exposed to albumin, mimicking proteinuria related damage.
  
  
  RESULTS
  VPAC1 expression was detected in the tubular proximal epithelial cells and in the glomerular podocytes of renal tissue from healthy and nephrotic children. Increased staining for PACAP was found in the proximal tubules of renal sections from children with NS compared to healthy renal sections. Expression and functionality of VPAC1 were demonstrated in HK-2 cells. Finally, PACAP did not alter cell viability or TGF-β1 expression of HK-2 cells exposed to albumin.
  
  
  CONCLUSIONS
  VPAC1 is the predominant receptor in the human kidney. The enhanced presence of PACAP in proximal tubular epithelial cells in nephrotic kidneys points to the reabsorption of filtered PACAP. On short term, PACAP has no in vitro effect on cell viability and TGF-β1 expression of proximal tubular epithelial cells exposed to high concentrations of albumin.
authors.affiliation: Pediatric Nephrology, Department of Development and Regeneration, University Hospitals of Leuven, Leuven, Belgium.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Eneman
authors.forename: Lambertus
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.forename: Chris
authors.initials: C
authors.lastname: Van Geet
authors.forename: Brigith
authors.initials: B
authors.lastname: Willemsen
authors.forename: Henry
authors.initials: H
authors.lastname: Dijkman
authors.forename: Elena
authors.initials: E
authors.lastname: Levtchenko
mesh_terms: D002461:Cell Line, Transformed; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide