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Cell Death Dis. 2016 Jun 23;7(6):e2272. doi: 10.1038/cddis.2016.171.

STAT3 modulates β-cell cycling in injured mouse pancreas and protects against DNA damage.

Author information

1
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium.
2
Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, Ghent, Belgium.
3
Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium.
4
Development and Stem Cells, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch 67404, France.
5
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.
6
Department of Clinical Chemistry and Radio-immunology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, Brussels 1090 Belgium.
7
Department of Endocrinology, UZ Brussel, Brussels 1090, Belgium.
8
ASZ Aalst, Aalst, Belgium.

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.

PMID:
27336716
PMCID:
PMC5143397
DOI:
10.1038/cddis.2016.171
[Indexed for MEDLINE]
Free PMC Article

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