PMID- 14733413
OWN - NLM
STAT- MEDLINE
DCOM- 20040304
LR  - 20161124
IS  - 1121-8428 (Print)
IS  - 1121-8428 (Linking)
VI  - 16
IP  - 5
DP  - 2003 Sep-Oct
TI  - Adrenomedullin inhibits pressure-induced mesangial MCP-1 expression through 
      activation of protein kinase A.
PG  - 673-81
AB  - In glomerular hypertension, monocyte chemoattractant protein-1 (MCP-1) has been 
      implicated in glomerulosclerosis progression. High-pressure load and stretch on 
      mesangial cells (MC) are two major effects of increased glomerular pressure. We 
      previously reported that pressure per se could induce MCP-1 expression in 
      cultured MC, suggesting the involvement of glomerular hypertension in renal 
      disease progression through MCP-1 expression in MC. We also showed that 
      adrenomedullin (AM) inhibited pressure-induced MC proliferation; however, it is 
      not clear whether AM alters pressure-induced mesangial MCP-1 expression. In this 
      study, we examined the effect of AM on pressure-induced MCP-1 expression in 
      cultured rat MC and the mechanism of such action. Using compressed helium, 
      pressure was applied to MC placed in a sealed chamber. AM inhibited 
      pressure-induced MCP-1 mRNA expression, measured by reverse 
      transcribed-polymerase chain reaction (RT-PCR), in a dose-dependent manner. This 
      inhibition was in parallel to an increase in cellular cyclic AMP (cAMP) levels 
      evoked by AM. The effects of forskolin and dibutyryl cAMP mimicked those of AM. 
      Protein kinase A (PKA) inhibitor H-89 significantly weakened the effects of AM. 
      AM significantly reduced the pressure-induced increase in MCP-1 protein in 
      supernatants of cultured MC, measured by enzyme-linked immunosorbent assay 
      (ELISA). Our results suggested that AM inhibits pressure-induced mesangial MCP-1 
      expression through PKA activation.
FAU - Iwamoto, Masako
AU  - Iwamoto M
AD  - The Second Department of Internal Medicine, School of Medicine, University of 
      Occupational and Environmental Health, Kitakyushu, Japan.
FAU - Osajima, Akihiko
AU  - Osajima A
FAU - Tamura, Masahito
AU  - Tamura M
FAU - Suda, Takeshi
AU  - Suda T
FAU - Ota, Takayuki
AU  - Ota T
FAU - Kanegae, Kaori
AU  - Kanegae K
FAU - Watanabe, Yuujiro
AU  - Watanabe Y
FAU - Kabashima, Narutoshi
AU  - Kabashima N
FAU - Anai, Hirofumi
AU  - Anai H
FAU - Nakashima, Yasuhide
AU  - Nakashima Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - J Nephrol
JT  - Journal of nephrology
JID - 9012268
RN  - 0 (Carrier Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Isoquinolines)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 0 (protein kinase modulator)
RN  - 148498-78-6 (Adrenomedullin)
RN  - 1F7A44V6OU (Colforsin)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
SB  - IM
MH  - Adrenomedullin
MH  - Animals
MH  - Bucladesine/pharmacology
MH  - Capillaries/physiopathology
MH  - Carrier Proteins/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Enzyme Activation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glomerular Mesangium/*metabolism
MH  - Hypertension, Renal/physiopathology
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Isoquinolines/pharmacology
MH  - Kidney Glomerulus/blood supply
MH  - Peptides/*pharmacology/physiology
MH  - Pressure
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Sulfonamides
EDAT- 2004/01/22 05:00
MHDA- 2004/03/05 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/03/05 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
PST - ppublish
SO  - J Nephrol. 2003 Sep-Oct;16(5):673-81.