The Effect And Mechanism Of Histone Methyltransferase MLL1 On Epithelial Mesenchymal Transition In Renal Tubular Epithelial Cells

Objective To investigate the effect of histone methyltransferase MLL1 on the pathogenesis and development of EMT during renal interstitial fibrosis induced by unilateral ureteral occlusion(UUO),and to explore its possible mechanism during epithelial mesenchymal transition(EMT).Method First,we established the rat UUO models and tested the expression of MLL1?E-cadherin?a-SMA?Vimentin and Col3a1 of rat tissue by Real time-PCR and Western blot respectively.Then,we used TGF-? stimulate normal HK-2 cells,and detected the expression of MLL1?E-cadherin?a-SMA?Vimentin and Col3a1 of cells by Real Time-PCR and Western blot to detect the best induced concentration of EMT by TGF-?.The last,HK-2 cells were pretreated with si RNA-MLL1 plasmids to inhibit the expression of MLL1 and then induced by TGF-?,then its expression levels of MLL1?a-SMA?Vimentin?E-cadherin?Col3a1 and H3K4me3 were detected by Western blot.At the same time,the expression of H3K4me3 in promoter region of EMT related genes was observed by Chromatin immunoprecipitation(Ch IP).Result Compared with normal and sham operated groups,the renal function of rats after UUO was lost with the increase in the obstruction time.Compared with normal and sham operated groups,the renal fibrosis was the most obvious and the expression of MLL1?E-cadherin?a-SMA?Vimentin and Col3a1 was highest when the rats underwent the UUO operation at 1W and 2W.In contrast with the normal group,the level of MLL1 reached the peak and the EMT of HK-2 induced by TGF-? was significantly when the concentration of TGF-? was 3ng/ml.Moreover,the EMT of HK-2 and the high level of H3K4me3 in the promoter region of a-SMA and Vimentin in HK-2 triggered by TGF-? were inhibited obviously by si RNA-MLL1 plasmids transfection.Conclusion MLL1 can force the occurrence of EMT induced by TGF-? in HK-2 cells,and the mechanism is to increase the expression of H3K4me3 in the promoter region of a-SMA and Vimentin.Therefore,this suggests that if the expression of MLL1 can be suppressed in the early stage of renal fibrosis,it may effectively delay the development of the EMT and the development of renal fibrosis.