Effects Of1,25-dihydroxy Vitamin D₃on TGF-β₁/smads Signaling Axis MRNA Expression In Rats With Renal Interstitial Obstruction

ObjectiveRenal tubular interstitial fibrosis process is one of the common pathological featuresin end-stage renal failure of the most kidney disease. TGF-β₁, the important cause offibrosis factor, plays an important role in the occurrence and development ofglomerular disease and renal tubular interstitial lesions.1,25-dihydroxyvitamin D₃,the biologically active metabolite of vitamin D₃after liver and kidney metabolismactivity, not only regulates calcium and phosphorus metabolism, but also has otherimportant biological effects in the kidney. This is a research to investigate theexpression and correlation of mRNA in the course of tubulointerstitial fibrosis inkidneys of young rats with unilateral ureteral obstruction （UUO） about TGF-β₁,Smad3and Smad7, meanwhile to determine the renal potential mechanisms of1,25-dihydroxyvitamin D₃after the treatment.MethodsA total of fifty-four male SD rats aged3to4weeks were served as experimentmodels. They were randomly divided into three groups: the sham operation group（n=18）, the model group after UUO （n=18） and1,25-dihydroxyvitamin D₃-treatedgroup after UUO（n=18）, in the latter of two of which the left urethral ligation wasperformed to construct unilateral ureteral obstruction model （UUO）. In addition, ratsin the1,25-dihydroxyvitamin D₃-treated group received1,25-dihydroxyvitamin D₃intragastric feeding （0.1ug/kg d） which was dissolved in peanut oil, while the shamoperation group and model group after UUO were given the same amount of peanut oil. The expression level of TGF-β₁mRNA, Smad3mRNA and Smad7mRNA weredetected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）at the3rd,7thand14thdays after experiments. All the datas of experiment wereanalyzed by statistics software SPSS17.0.Results（1） All production models with unilateral ureteral ligation were successful. Thevolume of obstruction side kidney was increased obviously, and the renal corticalwas thinner than the right kidney.（2） The mRNA expression of TGF-β₁, Smad3and Smad7in renal tissues of rats indifferent groups:①In the sham group, TGF-β₁mRNA and Smad3mRNA wereexpressed slightly, while Smad7mRNA was rich in expression. There was nodifference in all time points.②In UUO model untreated group, along with theextension of the times, the expression of TGF-β₁mRNA and Smad3mRNA weredramatically increased, while Smad7mRNA was decreased. Compared with thesham operation group, that had shown the more marked expression of TGF-β₁mRNA and Smad3mRNA yet attenuated Smad7express in the same time （allP<0.01）.③In the1,25-dihydroxyvitamin D₃-treated group, following theexperimental times extended, the expression of TGF-β₁mRNA and Smad3mRNA were decreased, while Smad7mRNA was increased. The expression ofTGF-β₁mRNA and Smad3mRNA were suppressed compared with the shamgroup, but not the UUO model group. The expression of Smad7mRNA washigher than the UUO model group, still lower than the sham operation group. Thedifference was significant at different time point （all P<0.01）.（3） Correlation analysis: Positive correlations were observed among the factor ofTGF-β₁and Smad3.They both have a negative correlations with the expression ofSmad7（all P<0.01）. ConclusionTGF-β₁/Smads signaling pathway may play an important regulating role in thepathogenesis of renal interstitial injury in young rats with UUO, which was promotedby TGF-β₁and Smad3yet retarded by Smad7. The protective effects of the1,25-dihydroxyvitamin D₃on the renal interstitial injury may partly be attribute to thedown-regulated expression of Smad3and up-regulated expression of Smad7.