title: Adrenomedullin reduces mesangial cell number and glomerular inflammation in experimental mesangioproliferative glomerulonephritis.
abstract: BACKGROUND
  Adrenomedullin (ADM) is a vasodilator peptide that is abundantly expressed in the kidney. ADM has antiproliferative effects on glomerular mesangial cells (MC) in vitro. Whether or not treatment with ADM can reduce MC proliferation in vivo [i.e., in mesangioproliferative glomerulonephritis (GN)] is unknown. We tested the hypothesis that ADM substitution reduces MC proliferation in GN.
  
  
  METHODS
  GN in rats was induced by injection of an anti-Thy-1.1 antibody. Rats received osmotic minipumps, which continuously delivered rat ADM (500 ng/hour, N = 11), or vehicle (N = 13) from day 3 to day 6 after GN induction. Rats were sacrificed 6 days after induction of GN. On kidney sections, cells staining positive for proliferating cell nuclear antigen, mesangial cells, monocytes, and apoptotic cells were counted. Parameters of inflammation and fibrosis were measured in renal cortex and sieved glomeruli by real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  Systolic blood pressure, diuresis, albuminuria, creatinine clearance, microaneurysm formation, and mesangial matrix expansion were not influenced by ADM infusion. However, ADM treatment significantly reduced the number of MC, showed a tendency to reduce total glomerular cell proliferation, and significantly increased apoptosis. ADM-treated GN animals showed significantly less glomerular monocyte infiltration. ADM treatment normalized transforming growth factor (TGF)-beta1 mRNA expression and reduced monocyte chemoattractant protein-1 (MCP-1), osteopontin, plasminogen activator inhibitor-1 (PAI-1), collagen I, and collagen III mRNA expression significantly.
  
  
  CONCLUSIONS
  Exogenous ADM infusion reduces MC number and glomerular monocyte infiltration in the state of mesangial proliferation during acute experimental mesangioproliferative GN. These findings indicate that ADM can influence the course of mesangioproliferative GN.
authors.affiliation: Department of Pediatrics, University Erlangen-Nuremberg, Germany. christian.plank@kinder.imed.uni-erlangen.de
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.forename: Bernd
authors.initials: B
authors.lastname: Klanke
authors.forename: Bettina
authors.initials: B
authors.lastname: Geissler
authors.forename: Markus
authors.initials: M
authors.lastname: Porst
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001835:Body Weight; D002452:Cell Count; D005355:Fibrosis; D005920:Glomerular Mesangium / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin