C-type natriuretic peptide inhibits proliferation and monocyte chemoattractant protein-1 secretion in cultured human mesangial cells

被引:21
作者
Osawa, H [1 ]
Yamabe, H [1 ]
Kaizuka, M [1 ]
Tamura, N [1 ]
Tsunoda, S [1 ]
Baba, Y [1 ]
Shirato, K [1 ]
Tateyama, F [1 ]
Okumura, K [1 ]
机构
[1] Hirosaki Univ, Sch Med, Dept Internal Med 2, Hirosaki, Aomori 0368562, Japan
来源
NEPHRON | 2000年 / 86卷 / 04期
关键词
C-type natriuretic peptide; glomerular mesangial cell; monocyte chemoattractant protein-1; natriuretic peptide receptor;
D O I
10.1159/000045836
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: Mesangial cell proliferation and matrix accumulation are hallmarks of various progressive glomerular diseases. We examined whether C-type natriuretic peptide (CNP) that is known to regulate the proliferation of vascular smooth muscle cells could modulate these pathological processes using human glomerular mesangial cells (GMCs) in culture. Methods: Proliferation of GMCs cultured with different concentrations of CNP-22 for 48 h was determined by a colorimetric assay using a tetrazorium salt, Monocyte chemoattractant protein-1 (MCP-1) and type IV collagen secretion into the culture media by GMCs in the presence or absence of CNP-22 were evaluated by ELISA. Expression of mRNA for natriuretic peptide receptor B (NPR-B), a specific receptor for CNP, was examined by reverse transcription polymerase chain reaction (RT-PCR). Results: CNP-22 (1-10 muM) inhibited serum-induced GMC growth in a dose-dependent manner. The amount of MCP-1 in the culture super natant was increased approximately 2.4-fold by 5 mug/ml of lipopolysaccharide. This increase was inhibited by CNP-22 at 0.1-1 muM in a dose-dependent fashion. CNP-22 (10 muM) inhibited GMC type IV collagen secretion stimulated by 20 ng/ml of platelet-derived growth factor. Expression of NPR-B mRNA was confirmed in GMCs by RT-PCR. Conclusions: CNP suppresses GMC proliferation and MCP-1 and type IV collagen secretion by GMCs. It may have a therapeutic potential against human proliferative glomerular diseases, especially those with the involvement of monocytes. Copyright (C) 2000 S. Karger AG, Basel.
引用
收藏
页码:467 / 472
页数:6
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