Aldosterone increases osteopontin gene expression in rat endothelial cells.
Aldosterone is currently recognized as one of the important risk hormones for cardiovascular disease. However, the cellular mechanism by which aldosterone affects the process of cardiovascular injury has not been well understood. In the present study, we investigated whether aldosterone induces pro-inflammatory genes expression in rat aortic endothelial cells. Aldosterone significantly increased steady-state osteopontin mRNA and protein levels, but not those of adhesion molecules or chemokine. The stimulatory effect of aldosterone on osteopontin expression was time-dependent (3-24h) and dose-dependent (10(-10)-10(-6)M), and abolished by a mineralocorticoid receptor (MR) antagonist spironolactone, but not by a glucocorticoid receptor antagonist RU486. The aldosterone-induced osteopontin mRNA expression was completely blocked by a transcription inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide. Thus, the present study demonstrated for the first time that aldosterone directly acts on endothelial cells to induce osteopontin gene expression via MR-mediated genomic action, which may be responsible for the initiation of inflammation and fibrosis in cardiovascular tissue induced by aldosterone.
Sugiyama
Toru
T
Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
Yoshimoto
Takanobu
T
Hirono
Yuki
Y
Suzuki
Noriko
N
Sakurada
Maya
M
Tsuchiya
Kyoichiro
K
Minami
Isao
I
Iwashima
Fumiko
F
Sakai
Haruna
H
Tateno
Toru
T
Sato
Ryuji
R
Hirata
Yukio
Y
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists; D053495:Osteopontin; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
D017931:DNA Primers; D000451:Mineralocorticoid Receptor Antagonists; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; D003513:Cycloheximide