Effect Of PPAR γ Activators On The Expression Of ICAM-1 And β₁ Integrin In Cultured Rat Glomerular Mesangial Cells Stimulated By High Glucose

OBJECTIVE: Diabetic nephropathy is one of important diabetic microvascular complications, which is characterized by glomerular matix accumulation, mesangial expansion and glomerulosclerosis. Mesangial cell plays important roles during these pathological processes. Present studies have proved that many factors involved in the pathogenesis of diabetic nephropathy,such as high glucose, hemodynamics and adhesion molecules. Recent studies have emphasized the important role of PPAR Y and its ligands in the pathophysiological processes. In order to explore the mechanism of PPAR Y in diabetic nephropathy and the relation between PPAR Y and adhesion molecules, we investigated the effect of PPAR Y activators -thiazolidinediones(Rosiglitazone) on the expression of ICAM-1 and β₁ integrin in cultured rat glomerular mesangial cells stimulated by high glucose.Methods: Cultured HBZY-1 rat glomerular mesangial cells were divided into 9 groups: Normol Glucose-treated group, High Glucose-treated group, Mannitiol-treated group, Normol and High Glucose along with different concerntration Rosiglitazone. Every group was treated for 24 hours. Theexpression of ICAM-1 was measured by immunohistochemistry. We alsomeasured the expression of Pi integrin by indirect immunofluorescencestaining and flow cytometry.RESULTS: l.Normol Glucose-treated group has expression of ICAM-1 andPi integrin.2.The expression of ICAM-1 and Pi integrin were increased in highglucose-treated group, there was no significant difference in mannitol-treatedgroup.3.The expression of ICAM-1 and Pi integrin in normol and high glucose-treated groups were decreased by adding different concerntration of Rosiglitazone.4.Following increasing concerntration of Rosiglitazone, the expression of ICAM-1 and Pi integrin in normol and high glucose-treated group were decreased more significantly. Compared to normol control group , the decreased degree of high glucose-treated group was more when the same concerntration Rosiglitazone was added.5. The expression of Pi integrin was positively correlated with ICAM-1. CONCLUSIONS: l.High glucose can increase significantly the expression of ICAM-1 and Pi integrin in cultured mesangial cells, which is independent of the osmotic. It suggests that adhesion mechanism involves in the pathogenesis of diabetic nephropathy.2. PPARy activators(Rosiglitazone) can inhibit the up-regulation of ICAM-1 and Pi integrin induced by high glucose in cultured mesangial cells,which is in a dose-dependent manner. The same effect was investigated in normol glucose-treated group. While the inhibition was more significantlyin high glucose-treated group. These data suggest that PPARy maybe effect mesangial expansion and glomerulosclerosis in diabetic nephropathy through involving in regulation of adhesion mechanism.