C-Type natriuretic peptide inhibits proliferation and monocyte chemoattractant protein-1 secretion in cultured human mesangial cells.
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 tetrazolium 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 microM) inhibited serum-induced GMC growth in a dose-dependent manner. The amount of MCP-1 in the culture supernatant was increased approximately 2.4-fold by 5 microg/ml of lipopolysaccharide. This increase was inhibited by CNP-22 at 0.1-1 microM in a dose-dependent fashion. CNP-22 (10 microM) 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.
Osawa
H
H
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan. osawa@cc.hirosaki-u.ac.jp
Yamabe
H
H
Kaizuka
M
M
Tamura
N
N
Tsunoda
S
S
Baba
Y
Y
Shirato
K
K
Tateyama
F
F
Okumura
K
K
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003470:Culture Media / Q000032:analysis; D003864:Depression, Chemical; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018932:Chemokine CCL2; D003470:Culture Media; D012333:RNA, Messenger; D020098:Natriuretic Peptide, C-Type; D003094:Collagen; D017461:Receptors, Atrial Natriuretic Factor