berberine reduces fibronectin expression by suppressing the s1p-s1p2 receptor pathway in experimental diabetic nephropathy models小檗碱降低纤连蛋白表达通过抑制s1p-s1p2受体途径在实验性糖尿病肾病模型.pdfVIP

Berberine Reduces Fibronectin Expression by Suppressing the S1P-S1P2 Receptor Pathway in Experimental Diabetic Nephropathy Models 1. 2. 3 1 1 1 1 Kaipeng Huang , Weihua Liu , Tian Lan , Xi Xie , Jing Peng , Juan Huang , Shaogui Wang , 1 1 1 Xiaoyan Shen , Peiqing Liu , Heqing Huang * 1 Laboratory of Pharmacology Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China, 2 Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of GuangZhou Medical University, Guangzhou, China, 3 Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China Abstract The accumulation of glomerular extracellular matrix (ECM) is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN) is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1)-sphingosine 1- phosphate (S1P) signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs) under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR) treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG) and simultaneous