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The antioxidative effect of bone morphogenetic protein-7 against high glucose-induced oxidative stress in mesangial cells |
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| Authors: | Ching-Hua Yeh Cheng-Kuei Chang Hung-Jung Lin |
| Institution: | a Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan City 70101, Taiwan b Department of Surgery, Mackay Memorial Hospital, Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei City 10401, Taiwan c Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City 70101, Taiwan d Department of Emergency Medicine and Department of Medical Research, Chi-Mei Medical Center, Yung Kang City, Tainan Shen 73101, Taiwan e Graduate Institute of Medical Sciences, Chang Jung Christian University, Kway Jen, Tainan Shen 71101, Taiwan |
| Abstract: | Bone morphogenetic protein-7 (BMP-7) protects kidneys from diabetic nephropathy (DN), and high glucose (HG)-induced oxidative stress is involved in DN. We investigated the antioxidative ability of BMP-7 using HG-treated mesangial cells. We treated rat mesangial cells (RMCs) with recombinant human BMP-7 (rhBMP-7) and examined changes in reactive oxygen species (ROS) levels and intracellular signals in response to HG-induced oxidative stress. rhBMP-7 decreased the level of ROS in HG-treated RMCs. In contrast, lowering endogenous BMP-7 by siRNA or BMP receptor II (BMP-RII) by anti-BMP-RII antibodies increased the level of ROS in HG-treated RMCs. rhBMP-7 increased Smad-1,5,8 phosphorylation, decreased PKCζ and c-Jun N-terminal kinase (JNK) phosphorylation, and decreased fibronectin and collagen IV synthesis in HG-treated RMCs. In conclusion, we found that BMP-7 could protect mesangial cells from HG-induced oxidative stress by activating BMP-RII. The antioxidative activity of BMP-7 was primarily due to inhibition of PKCζ, JNK phosphorylation, and c-jun activation. |
| Keywords: | BMP-7 Oxidative stress PKCζ Mesangial cells |
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