Bone marrow mesenchymal stem cell-derived exosomes improve renal fibrosis by reducing the polarisation of M1 and M2 macrophages through the activation of EP2 receptors

Renal fibrosis is the pathological outcome of most end-stage renal diseases, yet there are still limited therapeutic options for it. In recent years, bone marrow mesenchymal stem cell-derived exosomes (BM-MSCs) have received much attention. Here, we investigate the therapeutic effect of BM-MSCs on unilateral ureteral occlusion (UUO)-induced interstitial fibrosis in the kidney by modulating prostaglandin E2 receptor 2 (EP2). Renal pathological changes were evident in the UUO group compared to the control group, with significantly increased expression of α-smooth muscle actin (α-SMA), fibronectin, Ep2 and F4/80⁺ CD86⁺ and F4/80⁺ CD206⁺ cells in the UUO group (p< 0.05). Pathological changes were alleviated and F4/80⁺ CD86⁺ and F480/⁺ CD206⁺ cells were reduced after exosome or EP2 agonist intervention compared to the UUO group. These data were further confirmed in vitro. Compared to the lipopolysaccharide (LPS) group and the LPS + exosome + Ah6809 group, the lipopolysaccharide (LPS) + exosome group and the LPS + butaprost group showed a significant decrease in α-SMA expression, a decrease in the number of F4/80⁺ CD86⁺ and F4/80⁺ CD206⁺ cells, a decrease in interleukin (IL)-6 and an increase in IL-10 levels. Therefore, we conclude that BM-MSCs can reduce the polarization of M1 and M2 macrophages by activating EP2 receptors, thereby ameliorating renal fibrosis.