MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice
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...
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doaj-d1250936c6354424beb4a268b189ba712021-01-05T09:22:08ZengElsevierHeliyon2405-84402020-12-01612e05794MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in miceJordan Last0Max Brenner1Hao-Ting Yen2Monowar Aziz3Naomi-Liza Denning4Ping Wang5Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USACenter for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA; Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USACenter for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USACenter for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA; Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USACenter for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USACenter for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA; Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405844020326372Milk fat globule-epidermal growth factor-factor 8MFG-E8Renal ischemia-reperfusion injuryAcute kidney injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jordan Last Max Brenner Hao-Ting Yen Monowar Aziz Naomi-Liza Denning Ping Wang |
spellingShingle |
Jordan Last Max Brenner Hao-Ting Yen Monowar Aziz Naomi-Liza Denning Ping Wang MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice Heliyon Milk fat globule-epidermal growth factor-factor 8 MFG-E8 Renal ischemia-reperfusion injury Acute kidney injury |
author_facet |
Jordan Last Max Brenner Hao-Ting Yen Monowar Aziz Naomi-Liza Denning Ping Wang |
author_sort |
Jordan Last |
title |
MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice |
title_short |
MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice |
title_full |
MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice |
title_fullStr |
MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice |
title_full_unstemmed |
MFG-E8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice |
title_sort |
mfg-e8-derived peptide attenuates inflammation and injury after renal ischemia-reperfusion in mice |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2020-12-01 |
description |
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. |
topic |
Milk fat globule-epidermal growth factor-factor 8 MFG-E8 Renal ischemia-reperfusion injury Acute kidney injury |
url |
http://www.sciencedirect.com/science/article/pii/S2405844020326372 |
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