High glucose inhibits the survival of HRMCs and its mechanism

These findings suggested that high glucose inhibited the survival of HRMCs and may be associated with the downregulation of TIMP3 expression, Smad signaling pathway, inflammation and oxidative stress.

Cells were treated with high glucose (30 mM) or normal glucose (5 mM) for 48 hours. Cell proliferation was determined by trypan blue assay. The relative expression of metalloproteinase-3 (TIMP3) and inflammatory factors detected by real-time polymerase chain reaction (PCR). Protein expression of Smad2/3, p-Smad2/3 and Smad7 in HRMCs were analyzed by Western blot.

High glucose can promote the apoptosis of glomerular mesangial cells and cause diabetic nephropathy (DN). However, the mechanism remains unclear. In the present study, we investigated the effects of high glucose on the survival of human renal mesangial cells (HRMCs). Materials and

Compared with normal glucose, we found that high glucose significantly inhibited cell survival, accompanied by the decrease of tissue metalloproteinase-3 (TIMP3) mRNA expression. Western blot results showed that the expression of p-Smad2/3 was significantly up-regulated, the expression of Smad7 was significantly downregulated, and inflammatory factors IL-6/IL-8 mRNA expression were increased in the HRMCs cultured with the high glucose. We also found that, compared with the normal glucose, the level of MDA was significantly increased (p<0.01), and the level of SOD was significantly lower (p<0.05) in the HRMCs cultured with the high glucose. Conclusions: These findings suggested that high glucose inhibited the survival of HRMCs and may be associated with the downregulation of TIMP3 expression, Smad signaling pathway, inflammation and oxidative stress.