Abstract
Advanced glycation end products/advanced glycation end products receptor (AGEs/AGER) interaction triggers reactive oxygen species (ROS) generation and activates downstream signal pathways and induces apoptosis in endothelial progenitor cells. A number of studies have revealed the involvement of microRNAs (miRNAs) in regulating intracellular ROS production and apoptosis. However, few studies explore the role of miRNAs in regulating the effect of adipose tissue-derived stem cells (ADSCs) in repairing diabetic wound and the associated cellular mechanisms remain unclear. In this study, ADSCs were exposed to AGEs, then siRNA for AGER was transfected into ADSCs. We found that AGEs/AGER axis induced ROS generation and apoptosis in ADSCs. AGEs treatment downregulated miR-5591-5p in ADSCs, which directly targeted AGER. miR-5591-5p suppressed AGEs/AGER axis-mediated ROS generation and apoptosis in ADSCs in vitro. In addition, miR-5591-5p promoted cell survival and enhanced the ability of ADSCs for repairing cutaneous wound in vivo. Furthermore, we confirmed that c-jun kinase (JNK) signal was involved in the inhibitory effect of miR-5591-5p on AGEs/AGER axis-induced ROS generation and apoptosis in ADSCs. Thus, these results indicated that miR-5591-5p targeting AGEs/AGER/JNK signaling axis possibly regulates the effect of ADSCs in repairing diabetic wound.
Highlights
Adipose tissue-derived stem cells (ADSCs) are derived from adipose tissue stroma, which harbor the ability of self-renewal and differentiate into a number of functional cells[1]
To investigate whether Advanced glycation end products (AGEs) affect the expression of advanced glycation end products receptor (AGER) in adipose tissue-derived stem cells (ADSCs), cells were incubated with or without AGEs (100–1600 μg/ml) for 24 h, the expression of AGER was established by western blot and quantitative PCR
Previous studies indicate that AGEs/AGER interaction triggers reactive oxygen species (ROS) generation and activates downstream jun kinase (JNK) pathways and induce apoptosis in EPCs26
Summary
Adipose tissue-derived stem cells (ADSCs) are derived from adipose tissue stroma, which harbor the ability of self-renewal and differentiate into a number of functional cells[1]. ADSCs have been found to promote chronic wound healing[4]. Diabetic patients are much more susceptible to developing chronic wounds. ADSCs therapy could potentially influence the treatment of wounds in non-. Advanced glycation end products (AGEs) refer to a group of heterogeneous macromolecules that are produced by the post-translational modification of proteins via non-enzymatic glycation, lipids and nucleic acids, accumulate with age, and are abundantly elevated in diabetic patients[7]. The increased AGEs in diabetic patients cause a number of pathological changes. There has been evidence that elevated AGEs promotes apoptosis of endothelial progenitor cell (EPC) and endothelial cell inhibits proliferation of repairing cells, impedes wound healing[8,9,10].
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