PMID- 11703588
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20211203
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 60
IP  - 5
DP  - 2001 Nov
TI  - Pressure-induced expression of monocyte chemoattractant protein-1 through 
      activation of MAP kinase.
PG  - 1705-15
AB  - BACKGROUND: In glomerular hypertension, mesangial cells (MC) are subjected to at 
      least two physical forces: a high pressure and mechanical stretch. In 5/6 
      nephrectomized rat, a model of progressive glomerular sclerosis associated with 
      glomerular hypertension, monocyte chemoattractant protein-1 (MCP-1) is expressed 
      in glomeruli, suggesting the possible role of MCP-1 in the pathogenesis of 
      glomerular sclerosis; however, whether pressure directly affects MCP-1 expression 
      remains undetermined. Here we examined the effects of pressure on MCP-1 
      expression in cultured rat MC and the signal transduction pathways that lead to 
      MCP-1 expression. METHODS: Pressure was applied to MC by instilling compressed 
      helium gas into sealed plates. MCP-1 mRNA and protein levels in MC were detected 
      by reverse transcription-polymerase chain reaction (RT-PCR) or Northern blotting 
      and ELISA or Western blotting, respectively. Mitogen-activated protein (MAP) 
      kinase activity was measured with the catalytic activity of p42/p44 MAP kinase 
      and anti-phospho p42/p44 MAP kinase antibody. A transient transfection assay that 
      specifically modulates MAP kinase kinase (MEK) activity was carried out. RESULTS: 
      MCs subjected to external pressure expressed MCP-1 mRNA rapidly and transiently 
      with the peak level noted at 10 minutes and 80 mm Hg pressure. MCP-1 protein 
      levels in cell lysates and culture medium also significantly increased after 
      pressure loading. Pressure rapidly increased the phosphorylation level and 
      activity of p42/p44 MAP kinase. Treatment of MC with a MAP kinase kinase (MEK) 
      inhibitor, PD98059, suppressed levels of both pressure-induced MAP kinase 
      activities and MCP-1 mRNA expression. The constitutively activated type of MEK1 
      induced MCP-1 expression (13.7-fold) even in non-pressurized MC. CONCLUSIONS: Our 
      results indicate that pressure per se can induce MCP-1 via activation of MAP 
      kinase pathway, suggesting that glomerular hypertension might be involved in the 
      progression of renal diseases through the expression of MCP-1 in MC.
FAU - Suda, T
AU  - Suda T
AD  - The Second Department of Internal Medicine, University of Occupational and 
      Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi, Kitakyushu 
      807-8555, Japan.
FAU - Osajima, A
AU  - Osajima A
FAU - Tamura, M
AU  - Tamura M
FAU - Kato, H
AU  - Kato H
FAU - Iwamoto, M
AU  - Iwamoto M
FAU - Ota, T
AU  - Ota T
FAU - Kanegae, K
AU  - Kanegae K
FAU - Tanaka, H
AU  - Tanaka H
FAU - Anai, H
AU  - Anai H
FAU - Kabashima, N
AU  - Kabashima N
FAU - Okazaki, M
AU  - Okazaki M
FAU - Nakashima, Y
AU  - Nakashima Y
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 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Enzyme Activation
MH  - Glomerular Mesangium/*metabolism
MH  - MAP Kinase Kinase 1
MH  - Mitogen-Activated Protein Kinase 1/physiology
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinase Kinases/physiology
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Pressure
MH  - Protein Serine-Threonine Kinases/physiology
MH  - RNA, Messenger/*analysis
MH  - Rats
MH  - Rats, Wistar
EDAT- 2001/11/13 10:00
MHDA- 2002/01/11 10:01
CRDT- 2001/11/13 10:00
PHST- 2001/11/13 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/11/13 10:00 [entrez]
AID - S0085-2538(15)48051-2 [pii]
AID - 10.1046/j.1523-1755.2001.00012.x [doi]
PST - ppublish
SO  - Kidney Int. 2001 Nov;60(5):1705-15. doi: 10.1046/j.1523-1755.2001.00012.x.