Abstract
This study aimed to investigate the underlying mechanism of mesenchymal stem cells (MSCs) on protection of renal ischemia reperfusion injury (IRI). Exosomes originated from MSCs (MSC-ex) were extracted according to the instructions of Total Exosome Isolation Reagent. Rats were divided into five groups: sham-operated, IRI, MSC, MSC-ex, and MSC-ex + RNAase group. MSCs or MSC-ex were injected via carotid artery. The renal function test and pathological detection were applied to determine the renoprotection of MSC-ex on IRI. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to examine the levels of apoptosis-related proteins and inflammatory cytokines. Our results revealed that MSC-derived exosomes attenuated renal dysfunction, histologic damage, and decreased apoptosis. The expression levels of inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), and interferon gamma (IFN-γ), were decreased by the MSC-ex treatment. The expression levels of caspase-9, cleaved caspase-3, Bax, and Bcl-2 caused by IR were also inhibited by MSC-ex. MSC-ex + RNAase group shared the similar pattern of changes with IRI group, likely due to the ability of RNA hydrolase to eliminate the function of exosomes. Our results demonstrated that exosomes originating from MSCs have protective effects on IRI via inhibiting cell apoptosis and inflammatory responses. Out findings may provide a new insight into therapeutic mechanism of MSCs on renal IRI.
Highlights
Ischemia reperfusion injury (IRI), one of the major causes of post-operative renal allograft complications, is inevitable during transplantation [1, 2]
mesenchymal stem cells (MSCs) treatment and MSC-ex treatment decreased the levels of serum creatinine (SCr) (148 ± 16 μmol/L; 231 ± 30 μmol/L) and blood urea nitrogen (BUN) (20.49 ± 5.70 mmol/L; 31.36 ± 5.53 mmol/L), while this protective effect was not observed in the MSC-ex + RNAase group (Figure 1C)
The results demonstrated that rats that underwent renal ischemia reperfusion injury (IRI) had tissue injury, increased inflammatory cell infiltration, and larger areas of tubular necrosis, vacuolization and cast formation
Summary
Ischemia reperfusion injury (IRI), one of the major causes of post-operative renal allograft complications, is inevitable during transplantation [1, 2]. It has been reported that IRI may cause acute renal failure and delayed graft function, thereby impairing long-term survival of the graft and recovery in post-transplantation [3,4,5]. Mesenchymal stem cells (MSCs) have been found to exert several biological functions, such as repairing tissue damage, suppressing inflammatory responses, and modulating the immune system [6, 7]. They may protect acute kidney injury (AKI) induced by cisplatin, glycerol, and IRI in rats, the underlying mechanism has still remained elusive. The present study aimed to identify the protective effects and mechanism of MSC-ex on renal IRI
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