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

Partial pancreatic duct ligation (PDL) of mouse pancreas induces a doubling of the beta-cell mass mainly through proliferation of preexisting and newly formed beta-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 beta-cell proliferation were investigated. Duct ligation stimulates the expression of several cytokines that can act as ligands inducing STAT3 signaling and phosphorylation in beta-cells. beta-Cell cycling increased by conditional beta-cell-specific Stat3 knockout and decreased by STAT3 activation through administration of interleukin-6. In addition, the level of DNA damage in beta-cells of PDL pancreas increased after deletion of Stat3. These data indicate a role for STAT3 in maintaining a steady state in the beta-cell, by modulating its cell cycle and protection from DNA damage.