MicroRNA-149* Suppresses Hepatic Inflammatory Response Through Antagonizing STAT3 Signaling Pathway

Liver plays an important role in the body,is the place for biosynthesis,biotransformation,detoxification and a series of life activities.In vivo,the liver not only involved in sugar,lipids,protein and other substances metabolism,but also involved in the metabolic process of drugs,alcohol and toxic substances.Because many life activities are carried out in the liver,the liver is more likely to be invaded by pathogenic factors,such as drugs,microbial abnormal metabolism can cause liver damage,a large number of studies also confirmed that liver damage often accompanied by liver inflammation,cirrhosis,Liver fibrosis,severe cases can even cause liver failure and liver cancer.MicroRNA-149*(miRNA-149*)is a small molecule with a length of 22 bp.It binds to 3'UTR and 5'UTR to induce mRNA degradation and transcription inhibition,which affects the gene expression after transcription and regulates a series of life activities.The Stat3 signaling pathway is composed of the stat family proteins and plays an important role in regulating cell proliferation and migration.A series of studies shown that miRNA-149*is involved in the inhibition of liver inflammation by antagonizing the stat3 pathway.Mainly via mouse experiments,cell experiments to study the role of miRNA-149*on the liver inflammation.In the mouse experiment,mice were treated with LPS intraperitoneally.After 6 hours,the mice liver tissue was removed,RNA was extracted to do reverse transcription and real-time quantitative PCR.Compared with the parallel group,miRNA-149*can inhibit the expression of MMP-2,ICAM-1,C3,EGF(3 and IL-13 induced by LPS.Then extracted the protein of the liver tissue,determined the protein concentration,to do western blot,it can be seen miRNA-149*inhibit the phosphorylation of stat3 protein.Then the AST serum of the mouse serum,it can be seen in the LPS treated group mice whose miRNA-149*is knockout completely the aspartate transaminasen is higher.Finally,we used KI-67 and TUNEL to staine mouse tissue,we found that in the gene knockout mice,the apoptosis and proliferation of liver cells were more serious.Mice experiments revealed the reason is that miRNA-149*can inhibit liver inflammation.After transfection of miRNA-149*mimics and negative control into HepG2 cell,then used real-time quantitative PCR to dected the gene expression,we found the miRNA-149*inhibits reduced LPS-induced the expression of ICAM-2,IL-2,MMP9,TNF-a and or IL-6-induced the expression of the phosphorylation of stat3 protein.On the other hand we found that MCP-1,IL-6,MMP12,TGF? and IP-10 were inhibited by miRNA-149*.The results of mouse experiments and cell experiments show that miRNA-149*inhibits hepatic inflammation by antagonizing the stat3 pathway.So miRNA-149*can be used as a new target for the treatment of liver inflammatory drugs.