Effects of SAHA on Twist and HDAC1 expression in renal tissues of dia-betic rats / 中国病理生理杂志

ABSTRACT

AIM:To observe the effects of suberoylanilide hydroxamic acid(SAHA )on the expression of Twist,histone deacetylase 1(HDAC1),and the factors associated with epithelial-mesenchymal transition and extracellular matrix in diabetic rat renal tissues and its possible mechanism.METHODS:The rat model of diabetes mellitus(DM)was established by injection of streptozotocin.The rats were randomly divided into normal control(NC)group,DM group and SAHA group.When the model was successfully established for 8 weeks ,the rats in SAHA group were intragastrically trea-ted with SAHA at dose of 25 mg· kg-1 · d-1.After 8 weeks of treatment ,the rats were sacrificed.The biochemical pa-rameters and renal index were measured ,and the pathomorphological changes of the renal tissues were observed by HE and Masson staining.In addition ,the expression of Twist in renal tubular epithelial cells was evaluated by immunohistochemis -try.The protein levels of Twist,HDAC1,E-cadherin,α-SMA and collagen type Ⅳ(Col-Ⅳ)were determined by Western blot.The mRNA expression of Twist was detected by real-time PCR.RESULTS:The blood glucose ,24 h urine protein and kidney index in DM group were all obviously higher than those in NC group ,while kidney index was reduced in SAHA group as compared with DM group(P<0.05),but the blood glucose and 24 h urine protein markedly wasn't influenced by SAHA treatment.Compared with NC group,the mRNA and protein levels of Twist and protein levels of HDAC 1,α-SMA and Col-Ⅳwere increased in DM group(P<0.05),while they decreased in SAHA group as compared with DM group(P<0.05).The protein level of E-cadherin in NC group was higher than that in DM group ,and that was increased in SAHA group as compared with DM group(P<0.05).The correlation analysis showed that the Twist protein level was positively correlated with the HDAC1 protein level(P<0.05).CONCLUSION:SAHA decreases the expression of Twist and attenuates renal tubule fibrosis in DM rats by inhibiting the expression of HDAC 1 and Twist,thus promoting the tran-scription of E-cadherin.