ZIP8介导髓核细胞外基质降解的NF-κB信号通路机制研究

Abstract

The extracellular matrix (ECM) degradation of nucleus pulposus cells (NPCs) is mainly induced by metalloproteinases (MMPs). Zn 2+ is an essential component of MMPs, but the effect of Zn 2+ importers in controlling ECM metabolism remains unclear. The purpose of this research was to identify the involvement of Zn 2+ importers in ECM degradation induced by inflammatory stimuli and excessive mechanical stressing. In this study, NPCs from Sprague-Dawley (SD) rats were separated and cultured. FluoZin-3 AM staining was applied to detect [Zn 2+ ]i in NPCs treated with Interleukin-1β (IL-1β) or cyclic tensile strain (CTS) with a Flexcell Strain Unit. We found that intracellular Zn 2+ concentration ([Zn 2+ ]i) elevated dramatically, and ZIP8 is the predominant Zn 2+ importer among all importers in senescent NPCs. The [Zn 2+ ]i and MMP expression level both increased in IL-1β and CTS treated NPCs. Furthermore, the expression of ZIP8 was also markedly increased. However, knockdown of ZIP8 with siRNA alleviated ECM degradation induced by inflammatory stimuli and CTS. Both stimuli activated NF-κB signaling pathway , and knockdown of ZIP8 effectively inhibited NF-κB signaling pathway activation. In conclusion, knockdown of ZIP8 can alleviate NPCs’ ECM degradation caused by inflammatory stimuli and excessive mechanical stressing.