JAK2/STAT3 signaling pathway mediating proliferation and apoptosis of vascular smooth muscle cells in rats

Objective To investigate the relationship between STAT3 signal transduction pathway and proliferation as well as apotosis of vascular smooth muscle cells in rat.Methods VSMCs of rats were treated with AG490(a selective JAK2 inhibitor).MTT assay and flow cytometry were used to measure the proliferation and apoptosis.(RT-PCR) was performed to detect the levels of JAK2 mRNA expression from VSMCs.The expression of STAT3,(P-STAT3),JAK2,P-JAK2,cyclin D1 and BCL-2 proteins was measured by Western blot.Results High expression of JAK2 mRNA was detected in VSMCs and there was obvious decline of JAK2 mRNA after AG490 treating((P0.01)). AG490 inhibited the cell proliferation and induced apoptosis in a dose、time-dependent manner and resulted in significant downregulation of STAT3,P-STAT3,JAK2,P-JAK2,cyclin D1、BCL-2(P0.01).Conclusion Selective JAK2 inhibitor AG490 may inhibit the proliferation and induce apoptosis of VSMCs through decreasing expression of JAK2 mRNA.STAT3 Signaling pathway mediates JAK2-selective inhibitor-induced apoptosis and proliferative inhibition in VSMCs.This may be a new target of selective JAK2 inhibitor effect on VSMCs.