Abstract
Mesenchymal stem cells (MSCs) derived exosomes have been shown to have protective effects on the kidney in ischemia/reperfusion-induced renal injury. However, the key components in the exosomes and their potential mechanisms for the kidney protective effects are not well understood. In our current study, we focused on the abundant proteins in exosomes derived from MSCs (MSC-exo) and found that the C-C motif chemokine receptor-2 (CCR2) was expressed on MSC-exo with a high ability to bind to its ligand CCL2. We also proved that CCR2 high-expressed MSC-exo could reduce the concentration of free CCL2 and suppress its functions to recruit or activate macrophage. Further, knockdown of CCR2 expression on the MSC-exo greatly abolished these effects. Finally, we also found that CCR2 knockdown impaired the protective effects of MSC-exo for the renal ischemia/reperfusion injury in mouse. The results indicate that CCR2 expressed on MSC-exo may play a key role in inflammation regulation and renal injury repair by acting as a decoy to suppress CCL2 activity. Our study may cast new light on understanding the functions of the MSC-exo and these receptor proteins expressed on exosomes.
Highlights
Renal I/R (I/R) injury can be caused by renal transplantation, leading mainly to acute renal injury (AKI) [1]
Among the most differently expressed 5 proteins in the MSCexos compared to the NIH3T3-exos, we were interested in the two C-C motif chemokine receptor proteins, the CC motif chemokine receptor-1 (CCR1) and chemokine receptor-2 (CCR2)
By WB analysis, we found that both the two receptor proteins were highly expressed in the MSCexos and Mesenchymal stem cells (MSCs), but the CCR2 was much more abundant in the MSC-Derived Exosomes (MSC-exo) (Figure 1(b))
Summary
Renal I/R (I/R) injury can be caused by renal transplantation, leading mainly to acute renal injury (AKI) [1]. Despite the state-of-the-art advanced pharmaceutical therapy, AKI remains one of the major causes of morbidity and mortality in patients hospitalized for renal transplantation [2]. AKI is still a great threat for patients with acute renal I/R injury. There is a compelling need to find a new and safe therapeutic method for patients with acute renal I/R injury. Renal I/R always rapidly elicits a vigorous inflammatory reaction, inflammatory cell recruitment, cytokine production, and generation of free radicals and oxidative stress [8, 9]. These factors directly participate in further tissue damage after I/R injury [10, 11]. Inhibition of the inflammatory reaction is suggested to be pivotal for protecting the kidneys from acute I/R injury
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