MiR-128-3p mediates TNF-α-induced inflammatory responses by regulating Sirt1 expression in bone marrow mesenchymal stem cells

Tumor Necrosis Factor alpha (TNF-alpha), a multifunctional pro-inflammatory cytokine, is produced by macrophages/monocytes during acute inflammation, and plays a critical role in orchestrating the cytokine cascade in various inflammatory diseases. Previous studies demonstrated that TNF-alpha induces inflammatory responses in bone marrow mesenchymal stem cells (BMSCs) transplantation, leading to unsatisfactory effects and limit the clinical use of BMSCs. MicroRNAs are reported to involve in inflammation by regulating the expression of their targets in inflammatory response pathway. However, whether microRNAs mediate TNF-alpha-induced inflammatory responses in BMSCs remains elusive. Here, we found that TNF-alpha treatment induced an inflammatory response by increasing the levels of key inflammatory mediators, including IL-6, IL-1 beta, matrix metalloproteinase 9 (MMP9) and monocyte chemotactic protein-1 (MCP-1) in BMSCs. Moreover, real-time PCR result showed dramatically up-regulation of miR-128-3p after exposure to TNF-alpha. Interestingly, miR-128-3p over-expression exacerbated the TNF-alpha-induced inflammatory response, while suppression of miR-128-3p effectively eliminated the inflammatory response in BMSCs. Bioinformatic analysis identified sirtuin 1 is a direct target of miR-128-3p. Upregulation of sirtuin 1 induced by resveratrol also diminished the TNF-a-induced inflammatory response in BMSCs. Altogether, our results indicated that miR-128-3p targets sirtuin 1 to mediate the TNF-alpha-induced inflammatory response in BMSCs, which may provide new strategies to protect against inflammatory-dependent impairments in BMSCs. (C) 2019 Elsevier Inc. All rights reserved.