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- Title
Pressure-induced expression of monocyte chemoattractant protein-1 through activation of MAP kinase.
- Authors
Suda, Takeshi; Osajima, Akihiko; Tamura, Masahito; Kato, Hiroaki; Iwamoto, Masako; Ota, Takayuki; Kanegae, Kaori; Tanaka, Hiroshi; Anai, Hirofumi; Kabashima, Narutoshi; Okazaki, Masahiro; Nakashima, Yasuhide
- Abstract
Pressure-induced expression of monocyte chemoattractant protein-1 through activation of MAP kinase. 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...
- Subjects
MONOCYTES; MITOGENS; PROTEIN kinases
- Publication
Kidney International, 2001, Vol 60, Issue 5, p1705
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.00012.x