title: Gpr110 deficiency decelerates carcinogen-induced hepatocarcinogenesis via activation of the IL-6/STAT3 pathway.
abstract: Hepatocarcinogenesis is a complex process that includes pronounced necroinflammation, unregulated hepatocyte damage, subsequent extensive fibrosis, and carcinogenesis.GPR110was an adhesion G protein-coupled receptor. Analysis of the expression pattern ofGpr110in mice displayed thatGpr110was expressed highly in liver, implicating the tissue compartments where Gpr110 could execute its functions, the role of Gpr110 in the physiological and pathological state of liver remains unclear. Based on aGpr110knockout mouse model, we evaluated the role ofGpr110in hepatocarcinogenesis by using a carbon tetrachloride (CCl4)-induced liver injury and fibrosis model, as well as diethylnitrosamine (DEN) plus CCl4-induced liver cancer model. In this study, we found subdued chronic liver injury, reduced compensatory proliferation, lower liver fibrosis, but enhanced inflammation occurred inGpr110-/-mice during CCl4challenge. In addition,Gpr110-/-mice were resistant to liver tumorigenesis induced by DEN plus CCl4injection. Molecular mechanisms underlying these differences correlated with augmented activation of the IL-6/STAT3 pathway, which exerted hepatoprotective effects during liver damage, fibrosis, and oncogenesis inGpr110-/-mice. Furthermore, pharmacological inhibition of the activation of the IL-6/STAT3 pathway enhanced hepatic fibrosis and promoted DEN plus CCl4-induced carcinogenesis inGpr110-/-mice. In summary, absence ofGpr110decelerates liver fibrosis/cirrhosis progressing into tumorigenesis, due to strengthening activation of the IL-6/STAT3 pathway, leading to a weaker liver injury and fibrosis microenvironment. It is indicated that targeting Gpr110 and activating the IL-6/STAT3 pathway may be considered to be preventive methods for some cirrhosis transition.
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM)Shanghai 200025, China; Department of Medical Genetics, E-Institutes of Shanghai Universities, SJTUSMShanghai 200025, China.
authors.forename: Benting
authors.initials: B
authors.lastname: Ma
authors.affiliation: Thoracic Surgery Laboratory, Shanghai Pulmonary Hospital Affiliated to Tong Ji University School of Medicine Shanghai 200433, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai 200025, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai 200025, China.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai 200025, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai 200025, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM) Shanghai 200025, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shanghai Research Center for Model Organisms Shanghai 201203, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Shanghai Research Center for Model Organisms Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.affiliation: Department of Medical Genetics, E-Institutes of Shanghai Universities, SJTUSM Shanghai 200025, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM)Shanghai 200025, China; Department of Medical Genetics, E-Institutes of Shanghai Universities, SJTUSMShanghai 200025, China; Shanghai Research Center for Model OrganismsShanghai 201203, China.
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
keywords: CCl4; Gpr110; fibrosis; hepatocarcinogenesis; knockout mouse model