Effects of IKBα/NF-κB signaling pathway(activated by trans-tar-geted osteopontin)on cell autophagy,proliferation and cell cycle
Objective To explore the effects of IKBα/NF-κB signaling pathway activated by trans-targeted osteopontin(OPN)on the cell autophagy,proliferation and cell cycle of pulmonary artery smooth muscle cells(PASMCs)in hypoxic environment.Methods Rats PASMCs were cultured.The expressions of OPN and IKBα/NF-κB were ob-served in the PASMCs of hypoxia group.Lentiviruses with OPN(overexpressed or knocked down)were co-cultured with PASMCs,and the NF-κB inhibitor QNZ was added to PASMCs with OPN overexpression to interfere with the IKBα/NF-κB signaling pathway.The effects of OPN on autophagy were observed at the gene and protein levels.The number of autophagosomes was observed under electron microscopy.The effects of OPN on the cell prolifera-tion ability and cell cycle were detected by 5-ethynyl-2-deoxypyrimidine nucleoside assay and flow cytometry.Re-sults PASMCs in the hypoxia group expressed higher OPN than the normoxia group(P＜0.05),and NF-κB was higher in the hypoxia group than the normoxia group(P＜0.05).The normoxia group could inhibit autophagy pro-teins LC3B and Beclin1 by activating NF-κB through overexpression of OPN in PASMCs,and the addition of NF-κB inhibitor could promote the expression of autophagy proteins in PASMCs(P＜0.05).Interfering with the expres-sion of OPN in PASMCs in the hypoxia group could further promote the expression of autophagy proteins and au-tophagic vesicles(P＜0.05).The inhibition of OPN and NF-κB expression in PASMCs could block the cell transi-tion from G0/G1 phase to S phase and attenuate the proliferation induced by increased OPN(P＜0.05).Conclusion Trans-targeted OPN activates the IKBα/NF-κB signaling pathway.The activated IKBα/NF-KB signaling pathway affects the autophagy,proliferation,and cell cycle of PASMCs in hypoxic environment.
NETL
NSTL
万方数据
