Regulation Of Dot1l Expression By Aldosterone In Guinea Pig Cochlea

Objective:The pathogenesis of Meniere’s disease(MD)is not completely clear though it is well known that it’s pathophysiological basis is endolymphatic hydrops(EH).It has been shown that EH may be induced by aldosterone.We studied the histone H3 Lysine 79 methyltransferase Dot1l expression pattern and its’ regulation by aldosterone in guinea pig cochlea to clarify the possible role of Dot1l in EH and to search new clues for future investigation on pathogenesis and treatment of MD.Methods:Cochleas from 6 healthy adult guinea pigs with normal hearing identified by ABR were detected.Dotll expression pattern was studied by immunohistochemistry(IHC).Twenty-eight healthy adult guinea pigs with normal hearing were randomly divided into the control group and the treatment group.Aldosterone 1mg.kg-1.d-1 was injected intraperitoneally in animals in the treatment group and 20ul saline was down in those in the control groups for 7 days.Animals were sacrificed 1 month later following ABR examination.Histomorphology of cocholea was detected with HE,and Dot1l examined with IHC and western blot.Results:Dot1l was found in the stria vascularis,spiral ligament,Reissner’s membrane,spiral ganglion,organ of Corti,spiral limbus and outer salcus root cell.From basal turn to apical turn,Dotll expression in spiral ligament significantly decreased(P<0.01),while that in spiral ganglion significantly increased(P<0.05).There is no significant difference in ABR thresholds between the control group(18.57±6.02 dB SPL)and the treatment group(20.71±4.74 dB SPL).EH was found in 75%of animals in the treatment group,while no EH was found in the control group.Western blot showed that Dotll expression in the treatment group was significantly lower than that in the control group.IHC indicated that Dotll expression in the stria vascularis,spiral limbus,spiral ligament,organ of Corti was decreased by aldostrone.Conclusion:Histone H3 Lysine 79 methyltransferase Dotll exists in the cochlea of guinea pig.Aldosterone may induce endolymphatic hydrops by inhibiting Dotll expression.