Abstract
The senescence of mesenchymal stem cells (MSCs) plays a crucial role in the development and progression of systemic lupus erythematosus (SLE). Exosomes, small spherical bilayer proteolipid vesicles, contribute to the communication between various cells and their microenvironment by transferring information via their cargo, including the proteins, lipids, and RNAs. While exosomal miRNAs participate in various biological activities, correlations of circulating exosomes with senescent signs of BM-MSCs remain unclear. In our study, we aimed at exploring the roles of circulating exosomal miRNAs in the senescence of MSCs. We found that exosomes derived from SLE serum could increase the proportions of SA-β-gal positive cells, disorganize cytoskeletons, and reduce growth rates. Moreover, the expression of miR-146a declined significantly in serum exosomes of SLE patients compared with healthy controls. miR-146a could be internalized into MSCs via exosomes and participate in MSCs senescence through targeting TRAF6/NF-κB signaling. These results clarified the novel mechanism of MSCs senescence in SLE patients.
Highlights
Systemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease that affects multiple organs with poor quality of life and substantial mortality [1]
We previously reported that lipopolysaccharide (LPS) could accelerate senescence of dental pulp stem cells (DPSCs) by NF-κB-p53/p21 signaling pathway [8]
We found that the ratio of SAβ-gal positive BM-mesenchymal stem cells (MSCs) was upregulated significantly in the group treated with SLE serum, compared with ones treated with normal serum (Figures 1(a) and 1(b))
Summary
Systemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease that affects multiple organs with poor quality of life and substantial mortality [1]. Mesenchymal stem cell transplantation (MSCT) has been regarded as a safe and effective therapeutic approach. While allogenic MSCT conferred obvious therapeutic effects on SLE by previous studies, autologous MSCT was ineffective [3,4,5]. Our previous studies demonstrated that SLE BM-MSCs exhibited senescent characteristics and played a vital role in SLE. Reversing the senescent phenotype of BM-MSCs could improve therapeutic effects of autologous MSCT in SLE [6, 7]. Serum from SLE patients obviously promoted umbilical cord (UC) derived-MSCs senescence [10]. These data suggested that inflammation in microenvironment might participate in the senescence of MSCs, and we are required to further study and investigate the exact mechanism
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