The Mechanism Of KLF5 And Its Deacetylation In The Formation Of Barrett’s Esophagus

Background and purpose: Barrett’s esophagus(BE)refers to a pathological phenomenon of the esophagus,in which those with intestinal metaplasia are precancerous lesions of esophageal adenocarcinoma.The expression of intestinalization-related factor CDX2 is increased in Barrett’s esophagus,and KLF5 has an abnormal deacetylation status in Barrett’s esophagus.This article aims to explore the effect of the abnormal deacetylation status of transcription factor KLF5 on Barrett’s esophagus formation.Methods: The expression of KLF5 in BE tissues was detected by qRTPCR,western blot and immunohistochemistry,and the expression of acetylated KLF5 was detected by immunoprecipitation.The expression of IL-6,STAT3,KLF5 and CDX2 under the action of acid and/or bile acid mixture was detected by qRT-PCR and western blot.Then,KLF5 siRNA was transfected into HET-1A cells under the action of acid and/or bile acid mixture,and the expression of KLF5 and CDX2 protein was detected by western blot.The STAT3 overexpression plasmid and STAT3-siRNA were transfected into human squamous epithelial cells HET-1A cells,and the expression levels of STAT3 protein and KLF5 protein in the cells were detected by western blot technology.KLF5 overexpression plasmid was transfected in HET-1A cells to detect the expression of KLF5 and CDX2 proteins.Transfect HDAC1 overexpression plasmid and P300 overexpression plasmid in HET-1A cells to detect the protein expression level of acetylated KLF5.Results: Compared with the control group,the mRNA and protein expressions of IL-6,STAT3,KLF5,CDX2,and HDAC1 in BE tissues were all increased,but the level of acetylated KLF5 was decreased.It was found that the expression of IL-6,STAT3,KLF5 and CDX2 increased in HET-1A cells under the action of acid and / or bile acid mixture,and the expression of histone deacetylase HDAC-1 also increased.KLF5 siRNA can inhibit the expression of CDX2 in HET-1A cells caused by a mixture of acids and bile acids.Western blot results showed that the expression of KLF5 also increased after transfection of STAT3 overexpression plasmid into HET-1A cells;however,the silencing of STAT3 expression in HET-1A cells by siRNA can inhibit the expression of KLF5 protein in cells.KLF5 was up-regulated by KLF5 overexpression plasmid in HET-1A cells,and had no effect on CDX2 expression.After transfection of HDAC1 overexpression plasmids in HET-1A cells,co-immunoprecipitation and western blot showed that the expression of HDAC1 protein increased,and the level of acetylated KLF5 decreased at the same time,suggesting that increased expression of HDAC1 can inhibit the acetylation of KLF5.After transfection of the P300 overexpression plasmid,the level of acetylated KLF5 increased as P300 expression increased.Conclusion: In Barrett’s esophagus,STAT3 can regulate the expression of KLF5,which may be a bridge molecule between IL-6 / STAT3 and CDX2.The increased expression of KLF5 and its abnormal deacetylation status may be the key link in regulating the expression of CDX2 in squamous epithelial cells,thereby promoting the formation of Barrett’s esophagus(BE).