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Published on: September 26, 2018
Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys
Jiro Suzuki1, Fumio Otsuka, Yoshinori Matsumoto
1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Japan.
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.
Insights
Bone morphogenetic proteins (BMPs) may protect against kidney damage. Aldosterone and high salt activated BMPs in mice, suggesting a role in preventing glomerular injury.
Area of Science:
- Nephrology
- Molecular Biology
- Pathology
Background:
- Bone morphogenetic proteins (BMPs), especially BMP-7, show promise in inhibiting renal diseases.
- Previous in vitro studies indicated BMPs antagonize aldosterone-induced mesangial cell proliferation.
- The in vivo role of BMPs in aldosterone-induced renal glomerular injury requires further investigation.
Purpose of the Study:
- To investigate the in vivo roles of BMPs in aldosterone-induced renal glomerular injury.
- To explore the relationship between aldosterone, high salt intake, and BMP expression in the kidney.
- To understand the impact of mineralocorticoid receptor (MR) signaling on BMPs in glomerular injury.
Main Methods:
- BALB/c mice were treated with aldosterone injection and/or high-salt water for 9 weeks.
- Systemic parameters, kidney histology, and proteinuria were assessed.
- Immunohistochemistry and mRNA expression analysis were used to evaluate BMP-4, BMP-7, and MR levels.
Main Results:
- Aldosterone and high salt increased glomerular cellularity and diameter, despite no significant changes in blood pressure, body weight, kidney weight, or proteinuria.
- BMP-4 and BMP-7 were expressed in the glomerular mesangial region.
- Aldosterone and high salt enhanced BMP-4 and BMP-7 mRNA expression in the renal cortex, particularly after 9 weeks of treatment.
Conclusions:
- The renal BMP system is activated by aldosterone under high-salt conditions.
- This activation may play a protective role against aldosterone-induced glomerular damage in vivo.
- BMPs represent a potential therapeutic target for managing kidney injury.
