Abstract: ObjectiveTo examine the expressions of protein and mRNA related to Wnt/β-catenin signaling pathway in rats with experimental fluorosis.MethodsThirty-six healthy adult Sprague-Dawley(SD)rats were randomly divided into a control group(drinking water fluoride<1 mg/L),a low fluoride group(drinking water fluoride=5 mg/L),and a high fluoride group(drinking water fluoride=50 mg/L)(6 male and 6 female rats in each group).The occurrence of dental fluorosis in the rats was observed.The fluoride content in urine and bone was determined using fluoride ion selective electrode method.Renal function was tested using automatic biochemical analyzer.Pathological changes in renal tissues were observed with optical microscopy.The mRNA and protein expressions of Wnt4,b-catenin,E-cadherin in kidney tissues were detected with real-time fluorescent quantitative PCR(real-time PCR)and immunohistochemistry(IHC).ResultsThe overall detection rate of dental fluorosis in the fluoride-exposed rats was 83.3%(20/24)(75%9/12for the low fluoride group and 91.7%11/12for the high fluoride group).The urinary and bone fluoride concentrations increased with the increase of fluoride exposure(P<0.05)and the differences in the concentrations between the fluoride exposure groups and control group were significant(P<0.05).Creatinine and urea were significantly increased in the fluoride-exposed groups.Light microscopic observation found edema in tubular epithelial cells;luminal stenosis and obvious interstitial congestion of renal tubules were observed in the rats of fluoride-exposed groups and the damages in tubular epithelial cells aggravated with the increase of fluoride concentration.Protein expressions of Wnt4,β-catenin,and E-cadherin in the low fluoride group and high fluoride group were 7.78±1.17,6.66±0.59,and 3.23±0.82 and 17.46±3.18,12.46±0.89,and 1.23±0.35,respectively;and the mRNA expressions of the three proteins were 3.01±0.81,1.86±0.43,and 0.276±0.12 and 5.79±0.86,5.84±1.19,and 0.12±0.46,respectively.The immunohistochemistry and real-time fluorescent quantitive PCR showed that the protein and mRNA expressions of Wnt4 and b-catenin increased but those of E-cadherin decreased in kidney tissue of the rats of fluorosis group compared with those of the control group.ConclusionExcessive fluoride may activate Wnt signaling pathway and then induce epithelial-mesenchymal transdifferentiation(EMT)of renal tubules in rat.