PMID- 16105039
OWN - NLM
STAT- MEDLINE
DCOM- 20060111
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 68
IP  - 3
DP  - 2005 Sep
TI  - Adrenomedullin reduces mesangial cell number and glomerular inflammation in 
      experimental mesangioproliferative glomerulonephritis.
PG  - 1086-95
AB  - 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. CONCLUSION: 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.
FAU - Plank, Christian
AU  - Plank C
AD  - Department of Pediatrics, University Erlangen-Nuremberg, Germany. 
      christian.plank@kinder.imed.uni-erlangen.de
FAU - Hartner, Andrea
AU  - Hartner A
FAU - Klanke, Bernd
AU  - Klanke B
FAU - Geissler, Bettina
AU  - Geissler B
FAU - Porst, Markus
AU  - Porst M
FAU - Amann, Kerstin
AU  - Amann K
FAU - Hilgers, Karl F
AU  - Hilgers KF
FAU - Rascher, Wolfgang
AU  - Rascher W
FAU - Dotsch, Jorg
AU  - Dotsch J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Peptides)
RN  - 0 (Vasodilator Agents)
RN  - 148498-78-6 (Adrenomedullin)
SB  - IM
MH  - Adrenomedullin
MH  - Animals
MH  - Body Weight
MH  - Cell Count
MH  - Fibrosis
MH  - Glomerular Mesangium/drug effects/immunology/*pathology
MH  - Glomerulonephritis, Membranoproliferative/*drug therapy/immunology/*pathology
MH  - Male
MH  - Peptides/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Urine
MH  - Vasodilator Agents/*pharmacology
EDAT- 2005/08/18 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/08/18 09:00
PHST- 2005/08/18 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/08/18 09:00 [entrez]
AID - S0085-2538(15)50936-8 [pii]
AID - 10.1111/j.1523-1755.2005.00501.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Sep;68(3):1086-95. doi: 10.1111/j.1523-1755.2005.00501.x.