Abstract:

Objective     To explore effects of high glucose on expressions of connective tissue growth factor(CTGF)and its receptor-low density lipoprotein receptor related protein(LRP), and investigate the possible signaling pathway for modulation in cultured human mesangial cells(HMC) exposed to high glucose. Methods     Sandwich enzyme linked immunosorbent assay(ELISA)was employed to determine concentration changes of CTGF, phospho-extracellular signal-regulated kinase(pERK) and LPR in HMC culture solution in the normal glucose group, the high glucose group and the mannitol glucose group. Effects of high glucose on expressions of CTGF protein and its receptor LRP, and activation of the mitogen activated protein kinase(MAPKS)signaling pathway were observed． Results     Lower basal levels of CTGF protein were observed in cultured HMC. Higher levels of CTGF protein were detected in the high glucose group on the 1st day， reached a peak on the 3rd day(P<0.05), and then began to decrease on the 4th day(P>0.05)． The levels of CTGF in normal glucose and mannitol glucose groups did not notably change． A high glucose substratum induced the phosphorylation of ERK at the 1st hour，  reached a peak at 8h, maintained active at 824h, and then began to decrease to the basal level at 48h． However, no expression of pERK was detected in the normal glucose and mannitolglucose groups． Effect of high glucose on expression of CTGF protein was counteracted by intercepting phosphorylation of ERK with PD98059(a specific ERK activation inhibitor)． Also, high glucose did not affect expression of LRP protein in each group． Conclusion     High glucose influences expression of CTGF through the pERK-dependent signaling pathway in cultured HMC, while high glucose does not affect expression of LRP in HMC．

Key words: High glucose； Connective tissue growth factor； Low density lipoprotein receptor related protein； Human mesangial cells