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 lg 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.

Stimulation of Epithelial Sodium Channels in Endothelial Cells by Bone Morphogenetic Protein-4 Contributes to Salt-Sensitive Hypertension in Rats

“…It remains unclear how HS promotes 7 Oxidative Medicine and Cellular Longevity BMP4 expression. Previous studies have shown that aldosterone promotes BMP4 expression in the kidney [40]. Interestingly, we showed that the HS diet elevates plasma aldosterone in SS rats [22].…”

“…This argument is also supported by a previous study showing that BMP4 is expressed in endothelial cells and can induce endothelial dysfunction [39]. However, increased serum BMP4 may also come from other tissues, because HS intake stimulates the expression of BMP4 in renal cortex tissue [40]. It remains unclear how HS promotes 7 Oxidative Medicine and Cellular Longevity BMP4 expression.…”

“…Bath saline was as the same described for single-channel recordings, but with the addition of 10 mM D-glucose. The pipette solution contained (in mM): 40 10) was transfected in culture dishes with a HiTransG P infection enhancer (40 μL/mL). Sixteen hours after transfection, the complete medium was replaced, and the culture continued.…”

An in vivo role of bone morphogenetic protein-6 in aldosterone production by rat adrenal gland

“…Aldosterone breakthrough is the phenomenon by which circulating aldosterone concentrations increase above pretreatment levels after long-term therapy with angiotensin-converting enzyme inhibitors or Ang II type 1 receptor antagonists [19,20]. This phenomenon might have important clinical consequences since increased aldosterone in a high-salt state facilitates cardiovascular and renal damage in hypertensive conditions [21,22]. Involvement of various in vivo factors such as adrenocorticotropin, electrolytes, endothelins and Ang II type 2 receptor has been proposed to explain the aldosterone breakthrough phenomenon; however, the detailed underlying mechanism remains unknown [20,23,24].…”

Iron restriction inhibits renal injury in aldosterone/salt-induced hypertensive mice

“…17,18 Real-time reverse transcription-PCR assays were performed using the ABI PRISM 7900 with TaqMan Universal PCR Master Mix and TaqMan Gene Expression Assays (Applied Biosystems, Alameda, CA, USA). Real-time reverse transcription-PCR assays were performed using mouse specific primers for ferritin heavy chain 1 (Fth1; Mm0085070_g1), ferritin light chain 1 (Ftl1; Mm03030144_g1), and serum and glucocorticoid-regulated protein kinase 1 (SGK1; Mm00441387_g1).…”