BML-111 attenuates high glucose-induced inflammation, oxidative stress and reduces extracellular matrix accumulation via targeting Nrf2 in rat glomerular mesangial cells.
Diabetic nephropathy (DN) is the most paradigmatic complication of diabetes mellitus (DM) and brings about severe social and economic burdens. BML-111 is a potent agonist of Lipoxin A4 and has shown anti-inflammatory function in many diseases. The aim of the study is to investigate the effects of BML-111 on high glucose (HG) -induced mesangial cells. HBZY-1 cells were stimulated by HG with or without BML-111. ML385 was used as an Nrf2 inhibitor. Cell proliferation was measured by CC-K 8 assay. Besides, levels of TNF-α, IL-1, IL-6 and MCP-1 were detected by corresponding ELISA kits. DCFH-DA staining and an available ROS kit were employed to determine the ROS generation. In addition, extracellular matrix (ECM) accumulation was evaluated by immunofluorescence assay and western blot analysis. The protein expressions involved in Nrf2/HO-1 and MAPK pathway were assessed by western blot assay. Results indicated that BML-111 extremely inhibited HBZY-1 cell proliferation induced by HG. Moreover, BML-111 reduced the levels of TNF-α, IL-1, IL-6 and MCP-1, declined intracellular ROS level, and attenuated expression of ECM proteins laminin, fibronectin, collagen IV and TGF-β1. In addition, BML-111 promoted the activation of Nrf2, HO-1, and NQO1, while suppressed the phosphorylation of p38 and JNK. Further, NRF2 silence reversed the inhibitory effects of BML-111 on HG-induce inflammation, oxidative stress and ECM accumulation, accelerate the MAPK signaling, and diminished the expression of Nrf2 pathway. In summary, BML-111 alleviated HG-induced injury in HBZY-1 cells by repressing inflammatory response, oxidative stress and ECM accumulation via activating Nrf2 and inhibiting MAPK pathway.
['Wu|Xiaoming|X|', 'Pan|Congqing|C|', 'Chen|Rui|R|', 'Zhang|Shuo|S|', 'Zhai|Yangkui|Y|', 'Guo|Hang|H|']
D000818:Animals D000893:Anti-Inflammatory Agents D002460:Cell Line D003928:Diabetic Nephropathies D005109:Extracellular Matrix D005947:Glucose D006538:Heptanoic Acids D006801:Humans D007249:Inflammation D050527:Mesangial Cells D058990:Molecular Targeted Therapy D051267:NF-E2-Related Factor 2 D018384:Oxidative Stress D051381:Rats D015398:Signal Transduction
BML-111 Nrf2 Diabetic nephropathy High Glucose ECM