MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice. Issue 12 (December 2020)

• Record Type: Journal Article
• Authors: Last, Jordan; Brenner, Max; Yen, Hao-Ting; Aziz, Monowar; Denning, Naomi-Liza; Wang, Ping
• Is Part Of: Heliyon. Volume 6:Issue 12(2020)
• Publication Date: 2020-12
• Subjects: Milk fat globule-epidermal growth factor-factor 8 -- MFG-E8 -- Renal ischemia-reperfusion injury -- Acute kidney injury; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2020.e05794
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: 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. Abstract : Milk fat globule-epidermal growth factor-factor 8; MFG-E8; renal ischemia-reperfusion injury; Acute kidney Injury