title: STAT3 modulates β-cell cycling in injured mouse pancreas and protects against DNA damage.
abstract: Partial pancreatic duct ligation (PDL) of mouse pancreas induces a doubling of the β-cell mass mainly through proliferation of pre-existing and newly formed β-cells. The molecular mechanism governing this process is still largely unknown. Given the inflammatory nature of PDL and inflammation-induced signaling via the signal transducer and activator of transcription 3 (STAT3), the activation and the role of STAT3 in PDL-induced β-cell proliferation were investigated. Duct ligation stimulates the expression of several cytokines that can act as ligands inducing STAT3 signaling and phosphorylation in β-cells. β-Cell cycling increased by conditional β-cell-specific Stat3 knockout and decreased by STAT3 activation through administration of interleukin-6. In addition, the level of DNA damage in β-cells of PDL pancreas increased after deletion of Stat3. These data indicate a role for STAT3 in maintaining a steady state in the β-cell, by modulating its cell cycle and protection from DNA damage.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: De Groef
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Renmans
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Leuckx
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Roels
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.|Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, Ghent, Belgium.|Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Staels
authors.affiliation: Development and Stem Cells, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch 67404, France.
authors.forename: G
authors.initials: G
authors.lastname: Gradwohl
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.|Diabetes Center, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143-0669, USA.
authors.forename: L
authors.initials: L
authors.lastname: Baeyens
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Heremans
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.|Department of Clinical Chemistry and Radio-immunology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels 1090 Belgium.
authors.forename: G A
authors.initials: GA
authors.lastname: Martens
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.|Department of Endocrinology, UZ Brussel, Brussels 1090, Belgium.|ASZ Aalst, Aalst, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: De Leu
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Sojoodi
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Van de Casteele
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Heimberg
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004249:DNA Damage; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008026:Ligation; D008297:Male; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010183:Pancreatic Ducts / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D019394:Ki-67 Antigen; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor