title: RIG-I inhibits pancreatic β cell proliferation through competitive binding of activated Src.
abstract: Nutrition is a necessary condition for cell proliferation, including pancreatic β cells; however, over-nutrition, and the resulting obesity and glucolipotoxicity, is a risk factor for the development of Type 2 diabetes mellitus (DM), and causes inhibition of pancreatic β-cells proliferation and their loss of compensation for insulin resistance. Here, we showed that Retinoic acid (RA)-inducible gene I (RIG-I) responds to nutrient signals and induces loss of β cell mass through G1 cell cycle arrest. Risk factors for type 2 diabetes (e.g., glucolipotoxicity, TNF-α and LPS) activate Src in pancreatic β cells. Elevated RIG-I modulated the interaction of activated Src and STAT3 by competitive binding to STAT3. Elevated RIG-I downregulated the transcription of SKP2, and increased the stability and abundance of P27 protein in a STAT3-dependent manner, which was associated with inhibition of β cell growth elicited by Src. These results supported a role for RIG-I in β cell mass loss under conditions of metabolic surplus and suggested that RIG-I-induced blocking of Src/STAT3 signalling might be involved in G1 phase cycle arrest through the Skp2/P27 pathway in pancreatic β cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.|Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, Jiangsu, PR China.
authors.forename: GuangMing
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.|Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: HengGao
authors.initials: H
authors.lastname: Zhong
authors.affiliation: The Pre-clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing, PR China.
authors.forename: MeiJuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.
authors.forename: TingTing
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.
authors.forename: LiLi
authors.initials: L
authors.lastname: Gao
authors.affiliation: Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, PR China.
authors.forename: HuiWen
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008813:Mice, Inbred ICR; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019061:src-Family Kinases; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58