Effect of ubiquitin-proteasome pathway on expression of Smad7 in cultured glomerular mesangial cells induced by high concentration of glucose

AIM:To observe the expression of Smad7 and Smad ubiquition regulatory factor-Smurf2 in rat glomerular mesangial cells (GMC) stimulated by the high concentration of glucose, and to investigate the effect of the ubiquition on Smad signaling by adding MG132 as a proteasome differential inhibitor.METHODS:Cultured rat GMC were divided into normal group (the concentration of glucose:5.6 mmol/L), high glucose group (20 mmol/L, 30 mmol/L, respectively), therapy group (30 mmol/L glucose with MG132).The expressions of Smurf2 and Smad7 in each group were measured by indirect immunofluorescence and laser scanning confocal microscope.RESULTS:(1) The expression of Smurf2 in GMC in normal group was weak (25.93±3.35) whereas the expression of Smad7 was strong (64.09±7.43).(2) The expression of Smurf2 in high glucose group was stronger than that in normal group (P<0.05), in a concentration-dependent manner, 20 mmol/L high glucose (56.99±7.00), 30 mmol/L high glucose (96.36±9.19), respectively.The expression of Smad7 in high glucose group was weakened (P<0.05), 20 mmol/L high glucose (45.33±6.67), 30 mmol/L high glucose (30.20±4.41), respectively.(3) In therapy group, the expression of Smurf2 was found weakened and expression of Smad7 was enhanced.CONCLUSION:(1) High glucose increases the expression of Smurf2 and decreases the expression of Smad7 in glomerular mesangial cells.(2) Ubiquition-proteasome pathway (UPP) is related with the regulation of Smad signal transduction pathways in diabetic nephropathy.