The Role Of P38mapk On High-glucose Induced Icam-1 And Vcam-1 Expression In Mesangial Cell

Objective:Diabetic nephropathy is one of the most important microvascular complications of diabetes and the early changes of diabetic nephropathy are characterized by renal cells proliferation, hypertrophy and increased synthesis and accumulation of extracellular matrix, which ultimately result in glomerulosclerosis and tubulointerstitilal. Mesangial cell plays important roles in these pathological processes. Many factors involved in the pathogenesis of diabetic nephropathy, such as high glucose, hemodynamics and cytokine. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) are important adhesion molecules. Previous studies have shown that increased levels of ICAM-1 and VCAM-1 are associated with diabetic nephropathy. Recent studies have emphasized the important role of P38MAPK signal transduction pathways in the pathophysiological processes. In order to explore the roles of P38MAPK, ICAM-1 and VCAM-1 in diabetic nephropathy and the relations among P38MAPK, ICAM-1 and VCAM-1, we investigated the effect of high glucose and inhibitor of P38MAPK-SB203580 on the expression of P38MAPK, ICAM-1 and VCAM-1 in cultured rat glomerular mesangial cells and discuss the relations among P38MAPK, ICAM-1 and VCAM-1. We try to find new evidence for prevention and cure of diabetic nephropathy.Materials and Methods:Cultured rat glomerular mesangial cells in vitro were divided into four groups, glucose was a stimulated factor, SB203580 (inhibitor of P38MAPK) was an intervenor:Normal Glucose group (5.6mmol/1), High Glucose group (30mmol/1), SB203580 group (10umol/1 SB203580 and 30mmol/1 glucose) group, mannitol-treated group(25mmol/1 mannitol and 5.6mmol/1 glucose, as osmotic controls). We measured the expression of P38MAPK,ICAM-1 and VCAM-1 by Real time Quantitative PCR.Results: 1. mesangial cells of normal glucose group have expressions of P38MAPK,ICAM-1 and VCAM-1.2. The expressions of ICAM-1 mRNA and VCAM-1 mRNA were increased in high glucose group, which were dependent of time. But the expressions of ICAM-1 mRNA and VCAM-1 mRNA were invariable in mannitol group.3. The expression of P38MAPK mRNA was increased in high glucose group and mannitol group, and the expression of P38MAPK in high glucose group was higher than mannitol group, which is in a time-dependent manner.4. SB203580 can prevent the increased expression of ICAM-1 mRNA and VCAM-1 mRNA signigicantly induced by high glucose.Conclusion1. High glucose can significantly increase the expression of P38MAPK,ICAM-1 and VCAM-1 in GMCs, which is independent of the osmotic pressure.2. P38MAPK, ICAM-1 and VCAM-1 involves in the pathogenesis of diabetic nephropathy (DN).3. P38MAPK is upstream signaling molecule of ICAM-1 and VCAM-1, P38MAPK may affect diabetic nephtopathy by regulating the expression of ICAM-1 and VCAM-1.