The antioxidative effect of bone morphogenetic protein-7 against high glucose-induced oxidative stress in mesangial cells.
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 PKCzeta 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 PKCzeta, JNK phosphorylation, and c-jun activation.
Yeh
Ching-Hua
CH
Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
Chang
Cheng-Kuei
CK
Cheng
Meng-Fu
MF
Lin
Hung-Jung
HJ
Cheng
Juei-Tang
JT
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D002460:Cell Line; D019610:Cytoprotection; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000099221:Protein Kinase C zeta
D055419:Bone Morphogenetic Protein 7; D052006:Bone Morphogenetic Protein Receptors, Type II; D005947:Glucose; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D011493:Protein Kinase C; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D000099221:Protein Kinase C zeta; C525821:Bmp7 protein, rat