Opsonic Peptide MOP3 Attenuates Ischemic Acute Kidney Injury.

BACKGROUND

Renal ischemia/reperfusion (I/R) induced acute kidney injury (AKI) is a common and serious condition characterized by renal dysfunction, inflammation, tubular injury, and cell death. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that contributes to inflammation and tissue injury. MFG-E8-derived oligopeptide 3 (MOP3) is an opsonic peptide that binds eCIRP and promotes its phagocytic clearance. Here, we investigated the therapeutic effects of MOP3 in a murine model of renal I/R-induced AKI.

METHODS

Mice were subjected to 30 minutes of bilateral renal ischemia and treated with MOP3 or vehicle at the onset of reperfusion. Blood and kidney tissues were collected 20 h later. Renal inflammation, kidney function, tubular injury markers, histological damage, and cell death were assessed by RT-qPCR, biochemical assays, Western blotting, hematoxylin and eosin staining, and TUNEL staining.

RESULTS

MOP3 treatment reduced circulating eCIRP by 40% and renal IL-6, IL-1β, MIP-2, and KC mRNA expression by 43%, 84%, 73%, and 69%, respectively, compared with vehicle treatment. Serum urea nitrogen, creatinine, and NGAL levels were reduced by 56%, 63%, and 44%, respectively, after MOP3 treatment. MOP3 also decreased renal KIM-1 and NGAL mRNA expression by 88% and 44% and reduced their protein levels by 29% and 45%, respectively. Furthermore, MOP3 attenuated renal tubular injury and decreased TUNEL-positive cells.

CONCLUSIONS

These findings demonstrate that MOP3 attenuates inflammation, renal dysfunction, tubular injury, and cell death following renal I/R, suggesting that MOP3 may represent a promising therapeutic strategy for ischemic AKI.