title: Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys.
abstract: Recent studies have shown that bone morphogenetic proteins (BMPs), particularly BMP-7, have an inhibitory role in the development of various renal diseases. We previously reported antagonistic effects of BMPs on renal mesangial cell proliferation induced by aldosterone (Aldo) in vitro. In the present study, we investigated in vivo roles of BMPs in Aldo-induced renal glomerular injury. BALB/c mice aged 6 weeks were treated with Aldo injection (5 μg per day, intraperitoneally) and/or oral administration of high-salt (2%) water for 9 weeks. Systemic blood pressure, body weight, kidney weight and daily proteinuria were not significantly changed by Aldo and/or high-salt treatment. However, renal histological examination revealed increases in glomerular cellularity and glomerular diameter in the groups treated with Aldo injection and high-salt administration. Immunohistochemistry demonstrated expression of BMP-4 and -7 in the glomerular mesangial region. Aldo causes renal glomerular damage by stimulating mesangial cell proliferation and increasing extracellular matrix via the mineralocorticoid receptor (MR). MR messenger RNA (mRNA) expression in the renal cortex was transiently increased by 3-week treatment with Aldo and high-salt intake, but was decreased by 9-week treatment. Furthermore, the expression levels of BMP-4 and -7 mRNA were enhanced in the renal cortex treated with Aldo and high-salt administration. These findings suggest that the renal BMP system is activated by Aldo under the condition of high-salt exposure, which may have a key role in antagonizing glomerular damage in vivo.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Suzuki
authors.forename: Fumio
authors.initials: F
authors.lastname: Otsuka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inagaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Masaya
authors.initials: M
authors.lastname: Takeda
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsukamoto
authors.forename: Eri
authors.initials: E
authors.lastname: Nakamura
authors.forename: Kanako
authors.initials: K
authors.lastname: Ogura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000284:Administration, Oral; D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D000450:Aldosterone