Effects Of Advanced Glycation End Products On The Expression Of PEDF And VEGF In Cultured Human Renal Mesangial Cells

[OBJECTIVE] To observe expression of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in vitro human glomerular mesangial cells (HRMC) induced by advanced glycation end products (AGEs) and its possible mechanism, to further elucidate diabetic nephropathy pathogenesis.[METHODJVitro Human Renal Mesangial Cells treated by medium containing different doeses of AGE-BSA for different times, MTT method was used to detect cells proliferation; Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to detect VEGF and PEDF mRNA expression; Western bloting were used to detect VEGF、PEDF、and P-p38MAPK protein expression.[RESULTS]①Differernt concentrations of AGE-BSA mediate HRMC24h or AGE-BSA (200mg/L) mediate HRMC different times performance a role of promoting mesangial cell proliferation in certein cancentration range and in certein time range, and groups differences were statistically significant compared with the same concentration or time of BSA (P<0.05), and also compared to base control(P<0.05). However, all BSA groups has no influence on mesangial cell proliferation, has no statistically significant compared with base groups(P>0.05).②AGE-BSA in certein conteration and time range also showed a role of up-regulation of VEGF mRNA and protein expression, but down-regulation of PEDF mRNA and protein expression on mesangial cells. AGE-BSA groups have statistically significant compared with base groups (P<0.05).③Preincubate cells with specific inhibitor of p38MAPK-SB203580in concentration of lumol/L to10umol/L were in concentration manners inhibit the role of AGE-BSA mediate-VEGF increased, and the role of AGE-BSA mediate-PEDF decreased, thus improve the AGE-BSA mediated VEGF-to-PEDF unblanced expression.④Prestimulate cells with anti-RAGE (1～5mg/L) can block the role of AGE-BSA-mediated VEGF increased and and the role of AGE-BSA mediate-PEDF decreased, thus to improve the AGE-BSA-mediated decreased VEGF-to-PEDF ratio, and also block the role of AGE-BSA mediate-protein expression of P-p38MAPK increased on mesangial cells.[CONCLUTIONS](1)In certain cultured time concentration and time extent AGE-BSA promote mesangial cell proliferation, increase mRNA and protein expression of VEGF, however decrease mRNA and protein expression of PEDF.(2) AGE-BSA may be partly through the RAGE-p38MAPK pathway mediate up-regulation of VEGF and down-reguation of PEDF, participate in the pathogenesis of nephropathy.