MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice

• Main Authors: Jordan Last, Max Brenner, Hao-Ting Yen, Monowar Aziz, Naomi-Liza Denning, Ping Wang
• Format: Article
• Language: English
• Published: Elsevier 2020-12-01
• Series: Heliyon
• Subjects: Milk fat globule-epidermal growth factor-factor 8; MFG-E8; Renal ischemia-reperfusion injury; Acute kidney injury
• Online Access: http://www.sciencedirect.com/science/article/pii/S2405844020326372

Background: Renal ischemia-reperfusion (renal I/R) injury may lead to acute kidney injury (AKI). After renal I/R, proinflammatory mediators cause immune cell infiltration and further injury. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) is a protein involved in cell-cell and cell-matrix interactions. MSP68 is an MFG-E8-derived peptide that inhibits neutrophil adhesion and migration. Here, we evaluated whether MSP68 attenuates renal I/R injury. Materials and methods: Adult C57BL/6 mice were subjected to bilateral renal ischemia for 30 min followed by reperfusion and intraperitoneal administration of saline (vehicle) or MSP68 (5 mg/kg). Sham animals underwent laparotomy without renal I/R. The blood collected and studied for BUN, creatinine, and LDH by colorimetry. The kidneys were analyzed for IL-6 and TNFα by qPCR, ELISA, histological injury, and apoptosis by TUNEL. Results: At 24 h after surgery, serum levels of BUN, creatinine, and LDH were markedly higher in vehicle-treated renal I/R mice than in sham mice, but significantly lower in MSP68-treated renal I/R mice. Similarly, compared to sham, renal levels of IL-6 mRNA and protein and TNFα protein were markedly higher in vehicle-treated renal I/R mice, but significantly lower in MSP68-treated renal I/R mice. Vehicle-treated renal I/R mice also had severe renal tubular histological injury, which was significantly lower in MSP68-treated renal I/R mice. Additionally, the kidneys of vehicle-treated renal I/R mice had a 93-fold increase in TUNEL-positive cells, which were reduced by 35% in mice treated with MSP68. Conclusion: MSP68 has the potential to be developed as novel therapeutic agent for patients with AKI.