Effects Of Advanced Glycation End Products On Bioactivity Of Cultured Proximal Tubular Epithelial Cells

Aims: To investigate the effects of advanced glycation end products(AGEs) on survival/ metabolic activity and expression of connective tissue growth factor(CTGF) in human proximal tubular epithelial cells(PTEC); and the role in which molecular weight of AGEs plays.Methods: AGEs were isolated by gel chromatography; AGE peptides were digested from AGEs; and PTEC were cultured in Dulbecco modified Eagle medium(DMEM) and exposed to AGEs and agents. Cellular survival/metabolic activity were measured by methyl thiazolyl tetrazolium(MTT) and message RNA of CTGF and fibronectin(FN) were measured by reverse transcription polymerase chain reaction(RT-PCR).Results: AGEs induce a significant decrease in cellular survival/metabolic activity and an increase in expression of message RNA of CTGF and FN in a time- and dose-dependent manner, which can be inhibited by aminoguanidine and puerarin(P<0.05). CTGF antisense oligonucleotide can inhibit the expression of FN induced by AGEs(P<0.05). The bioactivity of AGE peptides is stronger than that of AGEs(P<0.05).Conclusions: AGEs decrease cellular survival/metabolic activity and upregulate CTGF mRNA in PTEC, which is negatively correlated with the molecular weight of AGEs and could be inhibited by aminoguanidine and puerarin. AGEs induce the expression of FN at least partly through CTGF, which may play an important role in renal interstitial fibrosis.