Involvement of signal transducer and activator of transcription 3 in delayed xenograft rejection in mice-to-rats cardiac transplantation as a regulator / 中华器官移植杂志

ABSTRACT

Objective To evaluate the roles of signal transducer and activator of transcription 3(STAT3) played in delayed xenograft rejection.Method Mice-to-rats cardiac xenograft model was established and recipients were administrated by inhibitor of phosphorylation of STAT3,5,15-Diphenylporphyrin(DPP),and immunosuppressive agent,ciclosporin A (CsA) alone or both.The survival of graft was analyzed.Immunohistochemistry and immunoblotting were utilized to detect the phosphorylated STAT3 (p-STAT3),and real-time polymerase chain reaction was used to assess STAT3-targeted genes in grafts.Result The expression of p-STAT3 was increased significantly with the prolonged survival in grafts (P ＜ 0.05).Administration of DPP and CsA both significantly prolonged survival of the grafts (P＜0.05),and decreased the expressions of STAT3-targeted genes including Bcl-xl,Bcl-2,Cyclin D1,C-myc and VEGF (P＜0.05).DPP and CsA exerted the synergistic effects.Conclusion STAT3,which is persistently activated in cardiac xenografts,probably up-regulates downstream genes to promote proliferation and to inhibit apoptosis of endothelial cells,leading to the activation of endothelial cells and delayed xenograft rejection.