Effect of all-trans retinoic acid on expression of MMPs and TIMPs in rats with glomerulosclerosis

Objective To investigate the effect of all-trans retinoic acid on the expression of MMPs and TIMPs in rats with glomerulosclerosis and its mechanism.Methods Eighty Wistar rats were divided into four groups randomly:sham operated group,model group,benazepril group and all-trans retinoic acid(ATRA)group(n=20,respectively).The glomerulosclerosis(GS)of rats were established by uninephrectomy and adriamycin injection through tail vien.Renal pathology was elvaluated at 12th week.Immunohistochemistry was performed for renal tissue to detect collagen Ⅳ(Col-Ⅳ)and fibronectin(FN).Real-time reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of MMP-2,MMP-9 and TIMP-1 mRNA.Results ATRA and benazepril reduced glomerular sclerosis index(P0.05,respectively)and significantly reduced Col-Ⅳ,FN protein expression and TIMP-1 mRNA expression compared to model group(P0.05).The expression of MMP-2,MMP-9 mRNA in ATRA and benazepril groups were enhanced obviously compared to model group(P0.05).There was no significant difference between ATRA and benazepril treatment group(P0.05).Conclusion ATRA can diminish the degree of glomerular sclerosis in GS rat model.The possible mechanism is through reducing the expression of TIMP-1,enhancing the expression of MMP-2 and MMP-9 resulting in the increase of extracellular matrix degradation in glomeruli.