title: Reg3g overexpression promotes β cell regeneration and induces immune tolerance in nonobese-diabetic mouse model.
abstract: The regenerating islet-derived gene was first isolated in regenerated pancreas tissues, greatly contributing to β cell regeneration. It is an anti-inflammatory in response to cellular stress. This encouraged us to investigate the exact role of a novel member of Reg family, regenerating islet-derived gene γ, in type 1 diabetes of nonobese-diabetic mice. For this, Reg3g gene was overexpressed in pancreatic islets, and conferred beneficial effects on β cell regeneration through activating the Janus kinase 2/signal transducer and activator of transcription 3/nuclear factor κB signaling pathway. Lentiviral vector-encoding regenerating islet-derived gene γ treatment also decreased lymphocyte infiltrates of the intra-islet and peri-islet by inducing both differentiation of regulatory T cell and immature dendritic cells of tolerogenic properties, which attenuated autoimmunity. This treatment further contributed to rebalanced levels of type 1/2 helper T cell cytokines and elevated α1-antitrypsin levels in the serum. These results were not observed in phosphate-buffered saline-treated mice or in lentivirus-control mice. We have shown, for the first time, to our knowledge, that regenerating islet-derived gene γ promotes β cell regeneration and preserves β cells from autoimmunity damage by increasing regulatory T cell differentiation and inducing tolerated dendritic cells. This regenerating islet-derived gene γ infusion could probably be developed into an optimal gene therapy for the prevention and reversal of type 1 diabetes.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
authors.forename: Fei
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
authors.forename: Jiao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, School of Life Science, Wuchang University of Technology, Wuhan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and tjphxm@aliyun.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D016086:Lentivirus / Q000378:metabolism; D016688:Mice, Inbred NOD; D000073718:Pancreatitis-Associated Proteins; D010641:Phenotype; D011506:Proteins / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D018417:Th1 Cells / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D000515:alpha 1-Antitrypsin
chemical_list: D016207:Cytokines; D007328:Insulin; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490255:Reg3g protein, mouse; D000515:alpha 1-Antitrypsin
keywords: dendritic cell; regulatory T cell; type 1 diabetes