Preliminary Study On The Mechanism Of Periostin In Alcoholic Fatty Liver In Mice

Excessive intake of alcohol will cause a variety of alcoholic diseases,of which alcoholic liver disease caused by alcohol is a serious menace to human health.In our previous experiments,we found that in the NIAAA model,there was a significantly increase of the expression of Periostin in the liver.However,after the deletion of Periostin,the accumulation of lipid droplets in the liver increased significantly and the liver was more seriously damaged.Therefore,we speculate that Periostin seems to play a protective role in alcoholic fatty liver disease.In this study,we further examine other indicators of liver injury,and find that the deletion of Periostin also aggravates the endoplasmic reticulum stress and causes more cell apoptosis,which also indicates that the liver injury of mice will be more serious if Periostin is knouted out.Therefore,the up-regulation of Periostin induced by alcohol should play a positive protective role in alcoholic liver disease.On this basis,we further explore the mechanism of Periostin up-regulation.Through database prediction,we find that the binding site of TFEB may exist in the promoter region of Periostin,suggesting that TFEB may play a certain regulatory role on Periostin.TFEB is a transcription factor that regulates the biogenesis of lysosomes and the binding of autophagosomes to lysosomes,and is closely related to alcoholic fatty liver disease.By testing,we find that not only in the NIAAA model,but also in AML 12 cell lines treated with alcohol,the expression levels of TFEB and its downstream target genes in both liver and cell lines are significantly up-regulated,and we find that TFEB dose play a certain regulatory role on Periostin promoter by Dual-lusiferase reporter assay.Therefore,we speculate that in alcoholic fatty liver diseases,TFEB may act as an upstream gene to regulate the expression of Periostin.In order to further explore the regulatory mechanism of Periostin on alcoholic liver disease,we start on screening the interacting proteins of Periostin to explore the downstream target genes or signal molecules of Periostin.We use a technology called proximity-dependent BioID approach.By means of molecular cloning and cell culture,we biologize the adjacent proteins around Periostin,then,enrich the biotinylated protins with NeutrAvidin agarose beads,and identify the proteins by mass spectrometry,so as to find candidate molecules around Periostin that may interact with it.After analysis,we obtain a total of 152 candidate proteins and perform some bioinformatics analysis in terms of cellular components,molecular functions,biological process and so on,which lay a foundation for further exploration of downstream signaling pathways and clarification of the mechanism of Periostin in alcoholic liver disease.