Milk fat globule-epidermal growth factor 8 (MFG-E8) attenuates sepsis-induced acute kidney injury by inhibiting NF-κB signaling pathway

Abstract

Purpose To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI). Methods Male C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway. Results MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-𝜅B signaling pathway in SAKI. Conclusion MFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.

MFG-E8 Maintains Cellular Homeostasis by Suppressing Endoplasmic Reticulum Stress in Pancreatic Exocrine Acinar Cells

“…However, whether the anti-inflammatory effect of MFG-E8 and the promotion of macrophage phagocytosis of apoptotic cells are related to the regulation of ER function remains unknown. Several studies have shown that MFG-E8 can directly regulate the NF-κB pathway (Zhao et al, 2019;Gong et al, 2020;Lu et al, 2021). In this study, we also found that MFG-E8 downregulated the NF-κB pathway.…”

Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

“…Previous studies have found that inflammation enhances and AS aggravates in mice lacking MERTK and MFGE8 ( Ait-Oufella et al, 2007 ; Cai et al, 2017 ; Triantafyllou et al, 2018 ). Several studies have shown that MFGE8 is a novel anti-inflammatory factor in multisystem diseases, such as neonatal sepsis, hepatic steatosis, rheumatoid arthritis and kidney injury ( Albus et al, 2016 ; Hansen et al, 2017 ; Zhao et al, 2019 ; Zhang et al, 2021 ). Additionally, MFGE8 level decreases in the CHD group and is negatively associated with the severity of coronary artery stenosis and the risk of clinical events ( Dai et al, 2014 ).…”

Multi-omics analysis of kidney tissue metabolome and proteome reveals the protective effect of sheep milk against adenine-induced chronic kidney disease in mice

“…82 Exogenous MFG-E8 may play a renoprotective role by inhibiting the NF-κB pathway to relieve renal inflammation and fibrosis levels in mice with sepsis. 83 Moreover, extracellular vesicles containing MFG-E8 alleviated renal fibrosis by inhibiting the RhoA/ROCK pathways in a rat model of renal fibrosis. 84 Therefore, the anti-fibrotic effect shown in sheep milk here may be related to the high content of anti-fibrotic substances, such as EGF.…”