The antioxidative effect of bone morphogenetic protein-7 against high glucose-induced oxidative stress in mesangial cells

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.