α<sub>2</sub>-Adrenoceptor agonist dexmedetomidine protects septic acute kidney injury through increasing BMP-7 and inhibiting HDAC2 and HDAC5
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- Chung-Hsi Hsing
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan;
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- Chiou-Feng Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan;
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- Edmund So
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan;
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- Ding-Ping Sun
- Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;
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- Tai-Chi Chen
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan;
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- Chien-Feng Li
- Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan;
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- Ching-Hua Yeh
- Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan, Taiwan; and
Description
<jats:p>Bone morphogenetic protein (BMP)-7 protects sepsis-induced acute kidney injury (AKI). Dexmedetomidine (DEX), an α<jats:sub>2</jats:sub>-adrenoceptor (α<jats:sub>2</jats:sub>-AR) agonist, has anti-inflammatory effects. We investigated the protective effects of DEX on sepsis-induced AKI and the expression of BMP-7 and histone deacetylases (HDACs). In vitro , the effects of DEX or trichostatin A (TSA, an HDAC inhibitor) on TNF-α, monocyte chemotactic protein (MCP-1), BMP-7, and HDAC mRNA expression in LPS-stimulated rat renal tubular epithelial NRK52E cells, was determined using real-time PCR. In vivo, mice were intraperitoneally injected with DEX (25 μg/kg) or saline immediately and 12 h after cecal ligation and puncture (CLP) surgery. Twenty-four hours after CLP, we examined kidney injury and renal TNF-α, MCP-1, BMP-7, and HDAC expression. Survival was monitored for 120 h. LPS increased HDAC2, HDAC5, TNF-α, and MCP-1 expression, but decreased BMP-7 expression in NRK52E cells. DEX treatment decreased the HDAC2, HDAC5, TNF-α, and MCP-1 expression, but increased BMP-7 and acetyl histone H3 expression, whose effects were blocked by yohimbine, an α<jats:sub>2</jats:sub>-AR antagonist. With DEX treatment, the LPS-induced TNF-α expression and cell death were attenuated in scRNAi-NRK52E but not BMP-7 RNAi-NRK52E cells. In CLP mice, DEX treatment increased survival and attenuated AKI. The expression of HDAC2, HDAC5, TNF-α, and MCP-1 mRNA in the kidneys of CLP mice was increased, but BMP-7 was decreased. However, DEX treatment reduced those changes. DEX reduces sepsis-induced AKI by decreasing TNF-α and MCP-1 and increasing BMP-7, which is associated with decreasing HDAC2 and HDAC5, as well as increasing acetyl histone H3.</jats:p>
Journal
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- American Journal of Physiology-Renal Physiology
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American Journal of Physiology-Renal Physiology 303 (10), F1443-F1453, 2012-11-15
American Physiological Society
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Details 詳細情報について
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- CRID
- 1360011145324283648
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- ISSN
- 15221466
- 1931857X
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- Data Source
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- Crossref